Cancer - cervix ... Worldwide, cervicalcancer is the third most common type of cancer in women. It is much less common in the United ... of the routine use of Pap smears . Cervicalcancer starts in the cells on the surface of ...

What is cervicalcancer screening? Cervicalcancer screening is used to find changes in the cells of the cervix that could lead to ... the FAQ Human Papillomavirus [HPV] Infection). How is cervicalcancer screening done? Cervicalcancer screening is simple and fast. ...

... the place where a baby grows during pregnancy. Cervicalcancer is caused by a virus called HPV. The ... for a long time, or have HIV infection. Cervicalcancer may not cause any symptoms at first. Later, ...

The epidemiologic data demonstrated by SEER clearly show a decrease of cervicalcancer over the decades due to widespread cervicalcancer screening with a pap smear, although there is currently a shift in the age distribution resulting in an increase of cervicalcancer among younger women, and a lower screening rate is a problem, particularly in Japan. Another peculiar trend is an increase of endocervical adenocarcinomas, and the underlying cause of this trend is still unknown. A screening program, employing the Bethesda system terminology and liquid-based cytology, combined with HPV DNA testing and p16(INK4a) immunohistochemistry/ cytochemistry, and a management guideline proposed by ASCCP, has been contributing to the early detection of cervicalcancers. However, it should be kept in mind that an HPV-targeted strategy is effective only for squamous lesions, which is mostly HPV-driven neoplasms, and that unusual HPV-negative adenocarcinomas, including gastric, clear cell, and mesonephric types, are a pitfall of HPV DNA testing and vaccination. Therefore, potential biomarkers, which can be applied for both squamous and glandular lesions, are awaited. The gastric type of adenocarcinoma of the cervix, a recently described subtype, is a distinct entity showing an aggressive clinical behavior, and, importantly, is estimated to be more frequent than in western countries. PMID:25151779

Background Cell lines have been used to study cancer for decades, but truly quantitative assessment of their performance as models is often lacking. We used gene expression profiling to quantitatively assess the gene expression of nine cell line models of cervicalcancer. Results We find a wide variation in the extent to which different cell culture models mimic late-stage invasive cervicalcancer biopsies. The lowest agreement was from monolayer HeLa cells, a common cervicalcancer model; the highest agreement was from primary epithelial cells, C4-I, and C4-II cell lines. In addition, HeLa and SiHa cell lines cultured in an organotypic environment increased their correlation to cervicalcancer significantly. We also find wide variation in agreement when we considered how well individual biological pathways model cervicalcancer. Cell lines with an anti-correlation to cervicalcancer were also identified and should be avoided. Conclusion Using gene expression profiling and quantitative analysis, we have characterized nine cell lines with respect to how well they serve as models of cervicalcancer. Applying this method to individual pathways, we identified the appropriateness of particular cell lines for studying specific pathways in cervicalcancer. This study will allow researchers to choose a cell line with the highest correlation to cervicalcancer at a pathway level. This method is applicable to other cancers and could be used to identify the appropriate cell line and growth condition to employ when studying other cancers. PMID:17493265

Background Cervicalcancer is a major mortality factor in the female population. This neoplastic is an excellent model for studying the mechanisms involved in cancer maintenance, because the Human Papilloma Virus (HPV) is the etiology factor in most cases. With the purpose of characterizing the effects of malignant transformation in cellular activity, proteomic studies constitute a reliable way to monitor the biological alterations induced by this disease. In this contextual scheme, a systemic description that enables the identification of the common events between cell lines of different origins, is required to distinguish the essence of carcinogenesis. Results With this study, we sought to achieve a systemic perspective of the common proteomic profile of six cervicalcancercell lines, both positive and negative for HPV, and which differ from the profile corresponding to the non-tumourgenic cell line, HaCaT. Our objectives were to identify common cellular events participating in cancer maintenance, as well as the establishment of a pipeline to work with proteomic-derived results. We analyzed by means of 2D SDS-PAGE and MALDI-TOF mass spectrometry the protein extracts of six cervicalcancercell lines, from which we identified a consensus of 66 proteins. We call this group of proteins, the "central core of cervicalcancer". Starting from this core set of proteins, we acquired a PPI network that pointed, through topological analysis, to some proteins that may well be playing a central role in the neoplastic process, such as 14-3-3?. In silico overrepresentation analysis of transcription factors pointed to the overexpression of c-Myc, Max and E2F1 as key transcription factors involved in orchestrating the neoplastic phenotype. Conclusions Our findings show that there is a "central core of cervicalcancer" protein expression pattern, and suggest that 14-3-3? is key to determine if the cell proliferates or dies. In addition, our bioinformatics analysis suggests that the neoplastic phenotype is governed by a non-canonical regulatory pathway. PMID:21696634

The effect of carbon nanowalls (CNWs) on the culturing rate and morphological control of cervicalcancercells (HeLa cells) was investigated. CNWs with different densities were grown using plasma-enhanced chemical vapor deposition and subjected to post-growth plasma treatment for modification of the surface terminations. Although the surface wettability of the CNWs was not significantly dependent on the CNW densities, the cell culturing rates were significantly dependent. Morphological changes of the cells were not significantly dependent on the density of CNWs. These results indicate that plasma-induced surface morphology and chemical terminations enable nanobio applications using carbon nanomaterials.

Background The mechanisms responsible for cervicalcancer radioresistance are still largely unexplored. The present study aimed to identify miRNAs associated with radioresistance of cervicalcancercells. Methods The radioresistant cervicalcancercell variants were established by repeated selection with irradiation. The miRNA profiles of radioresistant cells and their corresponding controls were analyzed and compared using microarray. Differentially expressed miRNAs were confirmed by quantitative real-time PCR. Cervicalcancercells were transfected with miRNA-specific mimics or inhibitors. Radiosensitivity of cervicalcancercells were determined using colony-forming assay. Results Among the differentially expressed miRNAs, 20 miRNAs showed the similar pattern of alteration (14 miRNAs were overexpressed whilst 6 were suppressed) in all three radioresistant cervicalcancercell variants compared to their controls. A miRNA signature consisting of 4 miRNAs (miR-630, miR-1246, miR-1290 and miR-3138) exhibited more than 5 folds of increase in radioresistant cells. Subsequent analysis revealed that these four miRNAs could be up-regulated in cervicalcancercells by radiation treatment in both time-dependent and dose-dependent manners. Ectopic expression of each of these 4 miRNAs can dramatically increase the survival fraction of irradiated cervicalcancercells. Moreover, inhibition of miR-630, one miRNA of the specific signature, could reverse radioresistance of cervicalcancercells. Conclusions The present study indicated that miRNA is involved in radioresistance of human cervicalcancercells and that a specific miRNA signature consisting of miR-630, miR-1246, miR-1290 and miR-3138 could promote radioresistance of cervicalcancercells. PMID:24283459

The human mitochondrial ATP-dependent Lon protease functions in regulating the metabolism and quality control of proteins and mitochondrial DNA (mtDNA). However, the role of Lon in cancer is not well understood. Therefore, this study was undertaken to investigate the importance of Lon in cervicalcancercells from patients and in established cell lines. Microarray analysis from 30 cancer and 10 normal cervical tissues were analyzed by immunohistochemistry for Lon protein levels. The expression of Lon was also examined by immunoblotting 16 fresh cervicalcancer tissues and their respective non-tumor cervical tissues. In all cases, Lon expression was significantly elevated in cervical carcinomas as compared to normal tissues. Augmented Lon expression in tissue microarrays did not vary between age, tumor-node-metastasis grades, or lymph node metastasis. Knocking down Lon in HeLa cervicalcancercells by lentivrial transduction resulted in a substantial decrease in both mRNA and protein levels. Such down-regulation of Lon expression significantly blocked HeLa cell proliferation. In addition, knocking down Lon resulted in decreased cellular bioenergetics as determined by measuring aerobic respiration and glycolysis using the Seahorse XF24 extracellular flux analyzer. Together, these data demonstrate that Lon plays a potential role in the oncogenesis of cervicalcancer, and may be a useful biomarker and target in the treatment of cervicalcancer. Lon; immunohistochemistry; cervicalcancer; cell proliferation; cellular bioenergetics. PMID:24260536

Gallic acid is a trihydroxybenzoic acid, also known as 3,4,5-trihydroxybenzoic acid, which is present in plants worldwide, including Chinese medicinal herbs. Gallic acid has been shown to have cytotoxic effects in certain cancercells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit human cervicalcancercell viability, proliferation and invasion and suppress cervicalcancercell-mediated angiogenesis. Treatment of HeLa and HTB-35 human cancercells with gallic acid decreased cell viability in a dose-dependent manner. BrdU proliferation and tube formation assays indicated that gallic acid significantly decreased human cervicalcancercell proliferation and tube formation in human umbilical vein endothelial cells, respectively. Additionally, gallic acid decreased HeLa and HTB-35 cell invasion in vitro. Western blot analysis demonstrated that the expression of ADAM17, EGFR, p-Akt and p-Erk was suppressed by gallic acid in the HeLa and HTB-35 cell lines. These data indicate that the suppression of ADAM17 and the downregulation of the EGFR, Akt/p-Akt and Erk/p-Erk signaling pathways may contribute to the suppression of cancer progression by Gallic acid. Gallic acid may be a valuable candidate for the treatment of cervicalcancer. PMID:24843386

Highlights: Black-Right-Pointing-Pointer Unknown cellular mutations complement papillomavirus-induced carcinogenesis. Black-Right-Pointing-Pointer Hedgehog pathway components are expressed by cervicalcancercells. Black-Right-Pointing-Pointer Hedgehog pathway activators and inhibitors regulate cervicalcancercell biology. Black-Right-Pointing-Pointer Cell immortalization by papillomavirus and activation of Hedgehog are independent. -- Abstract: Human papillomavirus (HPV) infection is considered to be a primary hit that causes cervicalcancer. However, infection with this agent, although needed, is not sufficient for a cancer to develop. Additional cellular changes are required to complement the action of HPV, but the precise nature of these changes is not clear. Here, we studied the function of the Hedgehog (Hh) signaling pathway in cervicalcancer. The Hh pathway can have a role in a number of cancers, including those of liver, lung and digestive tract. We found that components of the Hh pathway are expressed in several cervicalcancercell lines, indicating that there could exists an autocrine Hh signaling loop in these cells. Inhibition of Hh signaling reduces proliferation and survival of the cervicalcancercells and induces their apoptosis as seen by the up-regulation of the pro-apoptotic protein cleaved caspase 3. Our results indicate that Hh signaling is not induced directly by HPV-encoded proteins but rather that Hh-activating mutations are selected in cells initially immortalized by HPV. Sonic Hedgehog (Shh) ligand induces proliferation and promotes migration of the cervicalcancercells studied. Together, these results indicate pro-survival and protective roles of an activated Hh signaling pathway in cervicalcancer-derived cells, and suggest that inhibition of this pathway may be a therapeutic option in fighting cervicalcancer.

Conventional methods for cervicalcancer screening usually employ microscopic observations that may require fluorescence labeling of the cells, which could be time-consuming and expensive. Development of a novel method for cervicalcancercells determination in a rapid, label-free manner may significantly improve the cervicalcancer screening technique. Here two-dimensional (2D) light scattering patterns are obtained from yeast cells on a CMOS chip, where laser light is used to excite single cells via fiber-coupling under a microscope. Good agreements between the experimental and Mie theory simulation results convey that 2D light scattering patterns from cervicalcancercells may be obtained upon the apparatus developed here. Mie theory simulations on simplified normal and cancerouscervicalcells show that side scattering spectrum may be used for cervicalcancercells screening. Future experiments further convincing the 2D light scattering method proposed here may bring up a powerful technique that has profound applications in cervicalcancercell determination.

Using the genome editing tool known as CRISPR, Duke University researchers were able to selectively destroy two viral genes responsible for the growth and survival of cervical carcinoma cells, causing the cancercells to self-destruct.

Infection by carcinogenic human papillomaviruses (HPV) results in precancers [cervical intraepithelial neoplasia (CIN)] and cancers near the ectoendocervical squamocolumnar (SC) junction of the cervix. However, the specific cells targeted by HPV have not been identified and the cellular origin of cervicalcancer remains elusive. In this study, we uncovered a discrete population of SC junctional cells with unique morphology and gene-expression profile. We also demonstrated that the selected junctional biomarkers were expressed by a high percentage of high-grade CIN and cervicalcancers associated with carcinogenic HPVs but rarely in ectocervical/transformation zone CINs or those associated with noncarcinogenic HPVs. That the original SC junction immunophenotype was not regenerated at new SC junctions following excision, not induced by expression of viral oncoproteins in foreskin keratinocytes, and not seen in HPV-related precursors of the vagina, vulva, and penis further support the notion that junctional cells are the source of cervicalcancer. Taken together, our findings suggest that carcinogenic HPV-related CINs and cervicalcancers are linked to a small, discrete cell population that localizes to the SC junction of the cervix, expresses a unique gene expression signature, and is not regenerated after excision. The findings in this study uncover a potential target for cervicalcancer prevention, provide insight into the risk assessment of cervical lesions, and establish a model for elucidating the pathway to cervicalcancer following carcinogenic HPV infection. PMID:22689991

... Cancer found early may be easier to treat. Cervicalcancer screening is usually part of a woman's health ... may do more tests, such as a biopsy. Cervicalcancer screening has risks. The results can sometimes be ...

Malignant proliferation is the fundamental trait of tumor cells. The initiation of DNA replication represents a key process for cell proliferation, and has a marked impact on tumorigenesis and progression. Here we report that Sine oculis homeobox homolog 1 (SIX1) functions as a master regulator in DNA replication of cervicalcancercells. The expression of SIX1 was induced by the E7 oncoprotein of human papillomaviruses in cervical intraepithelial neoplasia and cervicalcancer. The increase of SIX1 expression resulted in the upregulation of multiple genes related to the initiation of DNA replication, including the genes coding for the proteins in minichromosome maintenance complex (MCM2, MCM3, MCM6), DNA polymerase ?-primase complex (POLA1, PRIM1, PRIM2), clamp loader (RFC3, RFC4, RFC5), DNA polymerase ? complex (POLD3) and DNA polymerase ? complex (POLE2). In line with this, the increase of SIX1 expression enhanced DNA synthesis, accelerated G1 to S phase progression, and promoted the proliferation of cervicalcancercells and the growth of cervicalcancer. Consistently, knockdown of SIX1 could hamper DNA synthesis, slow down G1 to S phase progression, and suppress tumor cell proliferation and tumor growth. Importantly, SIX1 could more efficiently promote anchorage-independent cell growth. These results suggest that the increase of SIX1 expression could promote tumorigenesis, progression and invasive growth of cervicalcancer by promoting DNA replication, and that targeting SIX1 may have significant therapeutic value in cervicalcancer treatment. PMID:24970368

Cervicalcancer, a potentially preventable disease, remains the second most common malignancy in women worldwide. Human papillomavirus (HPV) is the single most important etiological agent in cervicalcancer, contributing to neoplastic progression through the action of viral oncoproteins, mainly E6 and E7. Cervical screening programs using Pap smear testing have dramatically improved cervicalcancer incidence and reduced deaths, but cervicalcancer still remains a global health burden. The biomarker discovery for accurate detection and diagnosis of cervical carcinoma and its malignant precursors (collectively referred to as high-grade cervical disease) represents one of the current challenges in clinical medicine and cytopathology. PMID:19690652

Background Cervicalcancer is a major mortality factor in the female population. This neoplastic is an excellent model for studying the\\u000a mechanisms involved in cancer maintenance, because the Human Papilloma Virus (HPV) is the etiology factor in most cases. With\\u000a the purpose of characterizing the effects of malignant transformation in cellular activity, proteomic studies constitute a\\u000a reliable way to monitor the

Altered expression of specific microRNAs (miRNAs) has been observed in human cervicalcancer. However, the biological functions of many of these miRNAs are yet to be discovered. We previously showed that miR-944 is significantly more abundant in cervicalcancer tissues than their normal counterparts. In this study, we investigated the functions and targets of miR-944 in human cervicalcancercells. MiR-944 is located in the intron of the tumor protein p63 (TP63) gene, which is frequently overexpressed in cervical carcinomas. Using gain- and loss-of-function experiments in vitro, we demonstrate that miR-944 promotes cell proliferation, migration and invasion, but has no effect on apoptosis, in human cervicalcancercells. To identify the targets of miR-944, we performed photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation followed by deep sequencing. Among the candidate targets, we validated HECW2 (HECT domain ligase W2) and S100PBP (S100P binding protein) as direct targets of miR-944 using luciferase reporter assays and western blot analysis. Our findings reveal novel functions and targets of miR-944 in human cervicalcancercells, which may provide new insights of its role in cervical carcinogenesis. PMID:25156441

Smoking and CervicalCancer If you smoke, you have an increased chance of developing precancerous lesions of the cervix (called moderate or ... and an increase in the chance of developing cervicalcancer. Smoking greatly increases your risk for dysplasia and ...

In the network of chemokine signaling pathways, recent reports have described the SDF-1?/CXCR4 axis and its role in cancer progression and metastasis. Interestingly, we found downregulation of CXCR4 at both transcript and protein level in cervicalcancercell lines and primary tumors. We also found CXCR4 promoter hypermethylation in cervicalcancercell lines and primary biopsy samples. DNA hypomethylating drug 5-AZA-2?-deoxycytidine and histone deacetylase inhibitor Trichostatin A treatments in cell lines reactivate both CXCR4 transcription and protein expression. Cell adhesion assay demonstrated that autocrine SDF-1? promotes the loss of cell adhesion while paracrine SDF-1? predominantly protects the normal cervicalcells from loss of cell adhesion. Cervicalcancercell line C-33A having increased expression of CXCR4 after TSA treatment showed increased cell adhesion by paracrine source of SDF-1? in comparison to untreated C-33A. These findings demonstrate the first evidence that epigenetic silencing of CXCR4 makes the cells inefficient to respond to the paracrine source of SDF-1? leading to loss of cell adhesion, one of the key events in metastases and progression of the disease. Our results provide novel insight of SDF-1?/CXCR4 signaling in tumor microenvironment which may be promising to further delineate molecular mechanism of cervical carcinogenesis. PMID:25114911

High-risk human papillomaviruses (HPV) are the main etiologic factor for the development of cervicalcancer. Infections by these viruses have been detected in virtually all cervicalcancers. C-33A is one of the rare cervicalcancer derived cell lines considered as HPV-negative. Employing monoclonal antibodies raised against a conformational epitope of the HPV-16 E7 oncoprotein, we present evidence suggesting that E7-positive cells can be sporadically and transiently detected in C-33A cell cultures. Immunoblotting with affinity-purified rabbit polyclonal anti-HPV 16 E7 antisera and q-RT-PCR analysis suggest that these cells do probably not express HPV-16 E7. Moreover, we show that the HPV E7 protein level differs considerably between individual cells in cultures of several established cervicalcancercell lines. Our data suggest that expression of the E7 protein is variable in established cervicalcancercell lines including C-33A cells. PMID:25326774

Topical trans-retinoic acid treatment produced a statistically significant regression of cervical intraepithelial neoplasia (CIN) 2, but not CIN 3, in trials. A promising oral retinoid, 4-hydroxyphenylretinamide (4-HPR) induced apoptosis through non-retinoic acid-mediated pathways and is being studied in National Cancer Institute phase II trials in several organ sites. We studied the effects of 4-HPR on cervicalcancercell lines and on cervical epithelial cell lines immortalized by human papillomavirus (HPV). Four immortalized cervical epithelial cell lines (in vitro models of precancerous CIN lesions) and nine cervical carcinoma cell lines were studied. The growth inhibitory effect of 4-HPR was tested in monolayer culture and in semisolid medium, and concentrations required for a 50% growth inhibition within 5 days were determined. The agent 4-HPR inhibited the growth of cervical carcinoma cell lines and HPV-immortalized cell lines in a dose- and time-dependent fashion. Doses of 5 and 10 microM were more effective than 1 microM. The C33A cell line was most sensitive to 4-HPR, and HeLa and HT3 were the least sensitive. Of the HPV-immortalized cell lines, Z132, an HPV-16 immortalized cell line, was sensitive; the HPV 18-immortalized cell lines (Z173, Z183, and TCL-1) were not, although they were sensitive when grown in colonies. The agent 4-HPR is active against several cervicalcancercells lines and HPV-immortalized cervical epithelial cell lines. These findings are consistent with data from other laboratories studying other organ systems. This study helps establish a relevant biologically active dose for clinical trials in the cervix, one corresponding to the 5- and 10-microM tissue doses. PMID:12517593

Altered expression of specific microRNAs (miRNAs) has been observed in human cervicalcancer. However, the biological functions of many of these miRNAs are yet to be discovered. We previously showed that miR-944 is significantly more abundant in cervicalcancer tissues than their normal counterparts. In this study, we investigated the functions and targets of miR-944 in human cervicalcancercells. MiR-944 is located in the intron of the tumor protein p63 (TP63) gene, which is frequently overexpressed in cervical carcinomas. Using gain- and loss-of-function experiments in vitro, we demonstrate that miR-944 promotes cell proliferation, migration and invasion, but has no effect on apoptosis, in human cervicalcancercells. To identify the targets of miR-944, we performed photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation followed by deep sequencing. Among the candidate targets, we validated HECW2 (HECT domain ligase W2) and S100PBP (S100P binding protein) as direct targets of miR-944 using luciferase reporter assays and western blot analysis. Our findings reveal novel functions and targets of miR-944 in human cervicalcancercells, which may provide new insights of its role in cervical carcinogenesis. What's new? While miR-944 has been shown to be associated with tumor development and progression in several tumor types, its functions and targets remain undetermined. This study stands out as the first report of miR-944 functions and targets in human cancer. The authors demonstrate that miR-944 functions as an oncogene in human cervicalcancercells by promoting cell proliferation, migration, and invasion. In addition, they identified and validated HECW2 and S100PBP as direct targets of miR-944 in human cervicalcancercells. The findings provide new insights into the biological roles of miR-944 in human cervicalcancercells. PMID:25156441

Highlights: •miR-196a was overexpressed in cervicalcancer tissue compared to normal tissue. •miR-196a expression elevated proliferation and migration of cervicalcancercells. •miR-196a inhibited NTN4 expression by binding 3?-UTR region of NTN4 mRNA. •NTN4 inversely correlated with miR-196a expression in cervical tissue and cell line. •NTN4 expression was low in cervicalcancer tissue compared to normal tissue. -- Abstract: Recent research has uncovered tumor-suppressive and oncogenic potential of miR-196a in various tumors. However, the expression and mechanism of its function in cervicalcancer remains unclear. In this study, we assess relative expression of miR-196a in cervical premalignant lesions, cervicalcancer tissues, and four cancercell lines using quantitative real-time PCR. CaSki and HeLa cells were treated with miR-196a inhibitors, mimics, or pCDNA/miR-196a to investigate the role of miR-196a in cancercell proliferation and migration. We demonstrated that miR-196a was overexpressed in cervical intraepithelial neoplasia 2–3 and cervicalcancer tissue. Moreover, its expression contributes to the proliferation and migration of cervicalcancercells, whereas inhibiting its expression led to a reduction in proliferation and migration. Five candidate targets of miR-196a chosen by computational prediction and CervicalCancer Gene Database search were measured for their mRNA in both miR-196a-overexpressing and -depleted cancercells. Only netrin 4 (NTN4) expression displayed an inverse association with miR-196a. Fluorescent reporter assays revealed that miR-196a inhibited NTN4 expression by targeting one binding site in the 3?-untranslated region (3?-UTR) of NTN4 mRNA. Furthermore, qPCR and Western blot assays verified NTN4 expression was downregulated in cervicalcancer tissues compared to normal controls, and in vivo mRNA level of NTN4 inversely correlated with miR-196a expression. In summary, our findings provide new insights about the functional role of miR-196a in cervical carcinogenesis and suggested a potential use of miR-196a for clinical diagnosis and as a therapeutic target.

The Forkhead transcription factor FOXO1, an important downstream target of phosphatidylinositol-3-kinase (PI3K)/AKT signaling pathway, regulates cellular homeostasis by maintaining cell proliferation, apoptosis and viability in normal cells. Though, the function and regulation of FOXO1 is well documented in many cancers, the molecular mechanism of its regulation in cervicalcancer is largely unknown. In the present study we have investigated the role of PI3K inhibition on FOXO1 regulation. Expression profiling of primary tumors and cell lines show over expression of PIK3CA and AKT1; and down regulation of FOXO1. Lack of FOXO1 promoter methylation and inability of hypomethylating drug 5-Aza-2'-deoxycytidine and HDAC inhibitor trichostatin A to reactivate FOXO1 expression suggest that loss of FOXO1 expression is due to mechanisms other than promoter methylation/acetylation. Inhibition of PI3K by LY294002 decreased the level of p-AKT1 and activated FOXO1 transcription factor. We demonstrate that activation of FOXO1 induces apoptosis, cell proliferation arrest, and decreased cell viability in cervicalcancercell lines. Our data suggest that frequent down regulation of FOXO1 and its functional inactivation may be due to post-translational modifications in cervicalcancer. Together, these observations suggest that activation of FOXO1 and its nuclear sequestration is critical in the regulation of cell proliferation, cell viability and apoptosis in cervicalcancer. Hence, PI3K/AKT pathway may be a potential molecular target for cervicalcancer therapy. PMID:25157276

... part of your uterus (womb). What is a Pap smear? A Pap smear is a test your doctor does to check ... a series of changes. The results of your Pap smear can show whether your cells are going through ...

Treatment of advanced and relapsed cervicalcancer is frequently ineffective, due in large part to chemoresistance. To examine the pathways responsible, we employed the cervical carcinoma-derived SiHa and CaSki cells as cellular models of resistance and sensitivity, respectively, to treatment with chemotherapeutic agents, doxorubicin, and cisplatin. We compared the proteomic profiles of SiHa and CaSki cells and identified pathways with the potential to contribute to the differential response. We then extended these findings by comparing the expression level of genes involved in reactive oxygen species (ROS) metabolism through the use of a RT-PCR array. The analyses demonstrated that the resistant SiHa cells expressed higher levels of antioxidant enzymes. Decreasing or increasing oxidative stress led to protection or sensitization, respectively, in both cell lines, supporting the idea that cellular levels of oxidative stress affect responsiveness to treatment. Interestingly, doxorubicin and cisplatin induced different profiles of ROS, and these differences appear to contribute to the sensitivity to treatment displayed by cervicalcancercells. Overall, our findings demonstrate that cervicalcancercells display variable profiles with respect to their redox-generating and -adaptive systems, and that these different profiles have the potential to contribute to their responses to treatments with chemotherapy. PMID:25478571

Accumulating evidence supports the concept that cancer stem cells (CSCs) are responsible for the tumor recurrence and metastasis, the two major causes of cancer-related death. Therefore, CSC-targeted cancer therapy is important for the future development of more effective and advanced cancer therapy. One of the approaches is to specifically silence oncogene expression in CSCs and inhibit their growth. The significance of this approach is its specificity and ability to avoid multi-drug resistance of CSCs. In this chapter, we will describe a method of silencing HPV oncogenes E6/E7 in human cervical CSCs using HeLa cells as a model system. PMID:25348305

Human papillomavirus type 16 DNA and RNA were characterized in the cervicalcancer-derived CaSki cell line, which contains only integrated DNA, and in a cervicalcancer, which contains predominantly plasmid DNA. In both, a major RNA can code for the early open reading frame E7 and a minor one can code for E6. The cervicalcancer, but not the CaSki

Cervicalcancer has been identified as the third leading cause of average years of life lost per person dying of cancer. Since essentially all cervicalcancers contain copies of human papillomavirus (HPV) DNA, we propose a treatment that targets HPV-infected cells using strategies that re-introduce normal functions into the infected cells while sparing healthy cells. We propose the use of focused ultrasound in combination with microbubbles as means to deliver antibodies against the E6 protein present only in HPV positive cells. We conducted in vitro studies with cell cultures of SiHa cervical carcinoma cells seeded into Opticell™ chambers. An in-house ultrasound excitation apparatus was used to control and explore the optimal acoustic parameters in order to maximize delivery. We first validated the possibility of delivering the EX-EGFP-M02 vector (Genecopoeia) into the cells; 1.2 ?L of activated microbubbles (Definity®) and 50 ?g of the vector were mixed in media and then injected into the Opticell™ chamber. We used 32 ?s pulses at a central frequency of 930 KHz with a repetition frequency of 1.5 kHz and total exposure duration of 30 s; six pressure values were tested (0 to 1 MPa). Fluorescence imaging was used to determine the levels of intracellular proteins and assess delivery. The delivery of an anti-?-Tubulin antibody was next tested and confirmed that the delivery into HPV16 positive cells was successful.

Cervicalcancer is cancer that starts in the cervix. The cervix is the lower part of the uterus ( ... can do to decrease your chance of having cervicalcancer. Also, tests done by your health care provider ...

... often in black women than in white women. Human papillomavirus (HPV) infection is the major risk factor ... Although most women with cervicalcancer have the human papillomavirus (HPV) infection , not all women with an ...

This paper is to study the effect of traditional Chinese medicine monomer including quercetin, curcumin and Glaucocalyxin A on Hela cell of cervicalcancer. The inhibiting effect of quercetin, curcumin and Glaucocalyxin A on HeLa cells' proliferation is detected through using MTT method. Analysis for the effect of quercetin, curcumin and Glaucocalyxin A on proliferation cycle of Hela cell is performed through adopting flow cytometry. Three kinds of traditional Chinese medicine monomer can inhibit the growth of Hela cell, and they show dependent relationship between time and dose. Quercetin, curcumin and Glaucocalyxin A could inhibit cell proliferation, probably through making Hela cell be in stagnation and inducing its apoptosis. PMID:25016267

Panax ginseng is traditionally used as a remedy for cancer, inflammation, stress and aging, and ginsenoside-Rg5 is a major bioactive constituent of steamed ginseng. The present study aimed to evaluate whether ginsenoside-Rg5 had any marked cytotoxic, apoptotic or DNA-damaging effects in human cervicalcancercells. Five human cervicalcancercell lines (HeLa, MS751, C33A, Me180 and HT-3) were used to investigate the cytotoxicity of ginsenoside-Rg5 using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Additionally, the effects of ginsenoside-Rg5 on the apoptosis of HeLa and MS751 cells were detected using DNA ladder assays and flow cytometry. DNA damage was assessed in the HeLa and MS751 cells using alkaline comet assays and by detection of ?H2AX focus formation. The HeLa and MS751 cells were significantly more sensitive to ginsenoside-Rg5 treatment compared with the C-33A, HT-3 and Me180 cells. As expected, ginsenoside-Rg5 induced significant concentration- and time-dependent increases in apoptosis. In addition, ginsenoside-Rg5 induced significant concentration-dependent increases in the level of DNA damage compared with the negative control. Consistent with the comet assay data, the percentage of ?H2AX-positive HeLa and MS751 cells also revealed that ginsenoside-Rg5 caused DNA double-strands to break in a concentration-dependent manner. In conclusion, ginsenoside-Rg5 had marked genotoxic effects in the HeLa and MS751 cells and, thus, demonstrates potential as a genotoxic or cytotoxic drug for the treatment of cervicalcancer. PMID:25355274

Summary To investigate the relationship between the expression of cyclooxygenase-2 (COX-2) and menstrual cycle, the regulatory effects\\u000a of 17-?-estradiol (E2) and medroxyprogesterone acetate (MPA) on the expression of COX-2 in cervicalcancer Hela cells were examined. Cervicalcancer\\u000a specimens were obtained from 47 pre-menopausal patients. The phase of menstrual cycle was determined by case history and HE\\u000a staining of uterine endometrium.

Background Down regulation of genes coding for nucleoside transporters and drug metabolism responsible for uptake and metabolic activation of the nucleoside gemcitabine is related with acquired tumor resistance against this agent. Hydralazine has been shown to reverse doxorubicin resistance in a model of breast cancer. Here we wanted to investigate whether epigenetic mechanisms are responsible for acquiring resistance to gemcitabine and if hydralazine could restore gemcitabine sensitivity in cervicalcancercells. Methodology/Principal Findings The cervicalcancercell line CaLo cell line was cultured in the presence of increasing concentrations of gemcitabine. Down-regulation of hENT1 & dCK genes was observed in the resistant cells (CaLoGR) which was not associated with promoter methylation. Treatment with hydralazine reversed gemcitabine resistance and led to hENT1 and dCK gene reactivation in a DNA promoter methylation-independent manner. No changes in HDAC total activity nor in H3 and H4 acetylation at these promoters were observed. ChIP analysis showed H3K9m2 at hENT1 and dCK gene promoters which correlated with hyper-expression of G9A histone methyltransferase at RNA and protein level in the resistant cells. Hydralazine inhibited G9A methyltransferase activity in vitro and depletion of the G9A gene by iRNA restored gemcitabine sensitivity. Conclusions/Significance Our results demonstrate that acquired gemcitabine resistance is associated with DNA promoter methylation-independent hENT1 and dCK gene down-regulation and hyper-expression of G9A methyltransferase. Hydralazine reverts gemcitabine resistance in cervicalcancercells via inhibition of G9A histone methyltransferase. PMID:22427797

Cervicalcancer is the second most common cause of cancer in women and has a high mortality rate. Cisplatin, an antitumor agent, is generally used for its treatment. However, the administration of cisplatin is associated with side effects and intrinsic resistance. Morinda citrifolia (Noni), a natural plant product, has been shown to have anti-cancer properties. In this study, we used Noni, cisplatin, and the two in combination to study their cytotoxic and apoptosis-inducing effects in cervicalcancer HeLa and SiHa cell lines. We demonstrate here, that Noni/Cisplatin by themselves and their combination were able to induce apoptosis in both these cell lines. Cisplatin showed slightly higher cell killing as compared to Noni and their combination showed additive effects. The observed apoptosis appeared to be mediated particularly through the up-regulation of p53 and pro-apoptotic Bax proteins, as well as down- regulation of the anti-apoptotic Bcl-2, Bcl-XL proteins and survivin. Augmentation in the activity of caspase-9 and -3 was also observed, suggesting the involvement of the intrinsic mitochondrial pathway of apoptosis for both Noni and Cisplatin in HeLa and SiHa cell lines. PMID:23534730

Background Saponins of several herbs are known to induce apoptosis in many cancercells. The present study aimed to investigate the growth inhibitory effect of Paris saponin VII (PS VII), a kind of steroidal saponins from Chonglou (Rhizoma Paridis Chonglou), on the human cervicalcancercell line Hela and the relative molecular mechanisms. Methods Hela cells were exposed to different concentrations of PS VII (1 to 100 ?M). Inhibition of cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5-ethynyl-2?-deoxyuridine (EdU) assays. The amount of apoptotic cells was evaluated by flow cytometric analysis. And the protein level of cleaved caspase-3, cleaved caspase-9, Bax, and Bcl-2 was evaluated by Western blot. Results The half maximal inhibitory concentration (IC50) value of PS VII for the growth inhibition of Hela cells was 2.62?±?0.11 ?M. PS VII increased the expression of caspase-3, caspase-9, and Bax while decreased that of Bcl-2, suggesting that PS VII may induce apoptosis through intrinsic apoptotic ways. Conclusions These data indicate that PS VII has the potential for the treatment of cervicalcancer. PMID:25128382

The anticarcinogenic actions of epigallocatechin-3-gallate (EGCG), one of the main ingredients of green tea, against various cancer types including cervicalcancer are well documented. Studies pertaining to the exact molecular mechanism by which EGCG induces cancercell growth inhibition needs to be investigated extensively. In the present study, we observed a stupendous dose dependent reduction in the protein expression of Fused Toes Homolog (FTS) after treatment with EGCG at 1, 10, 25 and 50 ?M. Further, we were interested in finding out whether the decrease in the protein expression of FTS was due to decreased mRNA synthesis. Real time reverse transcriptase polymerase chain reaction results revealed a similar dose dependent reduction in the FTS mRNA after EGCG treatment. Chromatin immunoprecipitation analysis revealed the interaction between p53 and the promoter region of FTS. A dose dependent increase in this interaction was evidenced at 25 and 50 ?M EGCG treatment. p53 silencing increased the expression of FTS and also decreased the reduction in the levels of FTS expression after EGCG treatment. The decrease in the levels of FTS was more significant at 25 and 50 ?M and is associated with reduced physical interaction of FTS with Akt, phosphorylation of Akt and survival of HeLa cells. Collectively, these results conclude that EGCG induced anti-proliferative action in the cervicalcancercell involves reduced mRNA expression of FTS through p53. PMID:24065519

Objective Cervicalcancer is the third most common type of cancer in women worldwide and radiotherapy remains its predominant therapeutic treatment. Artesunate (ART), a derivative of artemisinin, has shown radiosensitization effect in previous studies. However, such effects of ART have not yet been revealed for cervicalcancercells. Methods The effect of ART on radiosensitivity of human cervicalcancercell lines HeLa and SiHa was assessed using the clonogenic assay. Cell cycle progression and apoptosis alterations were analyzed by flow cytometry. For in vivo study, HeLa or SiHa cells were inoculated into nude mice to establish tumors. Tissues from xenografts were obtained to detect the changes of microvessel density, apoptosis and cell cycle distribution. Microarray was used to analyze differentially expressed genes. Results ART increased the radiosensitivity of HeLa cells (SER =?1.43, P 0.001) but not of SiHa cells. Apoptosis and the G2-M phase transition induced by X-ray irradiation (IR) were enhanced by ART via increased Cyclin B1 expression in HeLa cells. Tumor growth of xenografts from HeLa but not SiHa cells was significantly inhibited by irradiation combined with ART (tumor volume reduction of 72.34% in IR?+?ART group vs. 41.22% in IR group in HeLa cells and 48.79% in IR?+?ART group vs. 44.03% in IR alone group in SiHa cells). Compared with the irradiated group, cell apoptosis was increased and the G2/M cell cycle arrest was enhanced in the group receiving irradiation combined with ART. Furthermore, compared with radiation alone, X-ray irradiation plus ART affected the expression of 203 genes that function in multiple pathways including RNA transport, the spliceosome, RNA degradation and p53 signaling. Conclusion ART potently abrogates the G2 checkpoint control in HeLa cells. ART can induce radiosensitivity of HeLa cells in vitro and in vivo. PMID:24666614

Physical changes of the cell surface of cells during transformation from normal to cancerous state are rather poorly studied. Here we describe our recent studies of such changes done on human cervical epithelial cells during their transformation from normal through infected with human papillomavirus type-16 (HPV-16), immortalized (precancerous), to cancerouscells. The changes were studied with the help of atomic force microscopy (AFM) and through the measurement of physical adhesion of fluorescent silica beads to the cell surface. Based on the adhesion experiments, we clearly see the difference in nonspecific adhesion which occurs at the stage of immortalization of cells, precancerous cells. The analysis done with the help of AFM shows that the difference observed comes presumably from the alteration of the cellular ``brush,'' a layer that surrounds cells and which consists of mostly microvilli, microridges, and glycocalyx. Further AFM analysis reveals the emergence of fractal scaling behavior on the surface of cells when normal cells turn into cancerous. The possible causes and potential significance of these observations will be discussed.

Purpose: To investigate the expression of p15INK4b, p16INK4a and p21Waf1/Cip1 in specimens from cases of normal cervical epithelium (NCE), cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC), and to evaluate whether there is evidence implicating oncogene-induced senescence (OIS) in cervical squamous cellcancer development. Methods: The immunohistochemical expression of p15INK4b, p16INK4a and p21Waf1/Cip1 were investigated in formalin-fixed paraffin-embedded specimens from 19 NCE, 51 CIN and 21 SCC cases, respectively. Comparisons among different groups for each marker were performed with Chi-square test. Results: The expression of p15INK4b, p16INK4a and p21Waf1/Cip1 were significantly higher in both CIN and SCC compared to NCE. Furthermore, the expression of p15INK4b and p21Waf1/Cip1 was significantly higher in CIN ? compared to CIN ?, and these expressions were statistically higher in CIN ? compared to CIN ?, respectively. The p16INK4a expression was significantly higher in CIN ? compared to CIN ?. Conclusions: The results suggested that the senescence programs mediated by p15INK4b, p16INK4a and p21Waf1/Cip1 were activated during the stage of CIN and SCC, and demonstrated that senescence may play important role in preventing from NCE to SCC.

Since uterine cervicalcancer is regarded as a radiosensive tumor, ionizing radiation is the most frequently used treatment modality against the disease. Although the crucial end-point is radiation-induced cell death, the tumors are not equally sensitive to radiation. Determining the criteria that may be used to predict tumor radiosensitivity is of importance; however, little success has been achieved thus far. In radioresistant cases the therapeutic strategy should be changed, thereby avoiding ineffective or unnecessary treatment. Furthermore, identification of the underlying molecular processes leading to radioresistance may lead to novel radiosensitising strategies. Cervical smears were obtained from seven patients with locally advanced cervicalcancer following each radiotherapy, and the radiation-induced damage of cancer tissue was examined by routine cytology. Since the formation of DNA double-strand breaks is considered critical for the cytocidal effect of radiation therapy, the molecular changes of the neoplastic cells were also assessed by laser scanning cytometry (LSC). Radiation-induced morphological changes of cancercells were evident at a dose of 7.2 Gy, whereas increased DNA content (or DNA index) was observed prior to the onset of morphological changes. Molecular change was detected earlier than the morphological change of the irradiated cancercells, indicating the feasibility of LSC in predicting the radiosensitivity of cervicalcancer tissue. PMID:25469269

Since uterine cervicalcancer is regarded as a radiosensive tumor, ionizing radiation is the most frequently used treatment modality against the disease. Although the crucial end-point is radiation-induced cell death, the tumors are not equally sensitive to radiation. Determining the criteria that may be used to predict tumor radiosensitivity is of importance; however, little success has been achieved thus far. In radioresistant cases the therapeutic strategy should be changed, thereby avoiding ineffective or unnecessary treatment. Furthermore, identification of the underlying molecular processes leading to radioresistance may lead to novel radiosensitising strategies. Cervical smears were obtained from seven patients with locally advanced cervicalcancer following each radiotherapy, and the radiation-induced damage of cancer tissue was examined by routine cytology. Since the formation of DNA double-strand breaks is considered critical for the cytocidal effect of radiation therapy, the molecular changes of the neoplastic cells were also assessed by laser scanning cytometry (LSC). Radiation-induced morphological changes of cancercells were evident at a dose of 7.2 Gy, whereas increased DNA content (or DNA index) was observed prior to the onset of morphological changes. Molecular change was detected earlier than the morphological change of the irradiated cancercells, indicating the feasibility of LSC in predicting the radiosensitivity of cervicalcancer tissue. PMID:25469269

Trichoderma spp. are known as a rich source of secondary metabolites with biological activity belonging to a variety of classes of chemical compounds. These fungi also are well known for their ability to produce a wide range of antibiotic substances and to parasitize other fungi. In search for new substances, which might act as anticancer agents, the overall objective of this study was to investigate the cytotoxic effects of Trichoderma harzianum and Trichoderma asperellum cultural filtrates against human cervical and breast cancercell lines (HeLa and MCF-7 cells respectively). To achieve this objective, cells were exposed to 20, 40, 60, 80 and 100 mg/ ml of both T. harzianum cultural filtrate (ThCF) and T. asperellum cultural filtrate (TaCF) for 24h, then the cell viability and the cytotoxic responses were assessed by using trypan blue and 3-(4,5-dimethylthiazol-2yl)- 2,5-biphenyl tetrazolium bromide (MTT) assays. Morphological changes in cells were investigated by phase contrast inverted microscopy. The results showed that ThCF and TaCF significantly reduce the cell viability, have cytotoxic effects and alter the cellular morphology of HeLa and MCF-7 cells in a concentration dependent manner. A concentration of 80 and 100mg/ml of ThCF resulted in a sharp decline in the cell viability percent of HeLa and MCF-7 respectively (25.2%, 26.5%) which was recorded by trypan blue assay. The half-maximal inhibitory concentrations (IC50) of ThCF and TaCF in HeLa and MCF-7 were recorded as 16.6, 12.0, 19.6 and 0.70 mg/ml respectively by MTT assay. These results revealed that ThCF and TaCF have a substantial ability to reduce the viability and proliferation of human cervical and breast cancercells. PMID:25227819

... pre-cancers are treated Next Topic Additional resources Cervicalcancer prevention and screening: Financial issues Financial issues can ... to tell you up front. National Breast and CervicalCancer Early Detection Program All states are making cervical ...

A major agenda for tumor immunology is the generation of specific immune responses leading to the destruction of incipient and frank neoplasia. In this report, we show that a novel HPV16 E7 fusion protein can produce objective therapeutic responses against incipient cervicalcancer in genetically engineered mice that express in the cervix the HPV16 early region genes implicated as causative agents in human cervicalcancer. Although nonresponsive toward the HPV16 E7 oncoprotein in the CD8+ T-cell compartment by virtue of MHC haplotype, the mice were capable of mounting an induced CD4+ T-cell response against E7, and in addition developed spontaneous anti-E7 antibodies. HPV16/CD4-/- mice showed increased tumor burden indicative of CD4-mediated immune surveillance. Seeking to enhance the CD4 response, we immunized mice bearing incipient cervicalcancer with a recombinant protein fusing E7 with a mycobacterial heat shock protein. The incidences of cervical carcinoma and of high-grade dysplasia (CIN 3) were consequently reduced by comparison to control mice. Thus, an HPV16 E7 immunogen holds promise for noninvasive treatment and prevention of human cervicalcancer. PMID:15753402

Currently, taxol is mainly extracted from the bark of yews; however, this method can not meet its increasing demand on the market because yews grow very slowly and are a rare and endangered species belonging to first- level conservation plants. Recently, increasing efforts have been made to develop alternative means of taxol production; microbe fermentation would be a very promising method to increase the production scale of taxol. To determine the activities of the taxol extracted from endophytic fungus N. sylviforme HDFS4-26 in inhibiting the growth and causing the apoptosis of cancercells, on comparison with the taxol extracted from the bark of yew, we used cellular morphology, cell counting kit (CCK-8) assay, staining (HO33258/PI and Giemsa), DNA agarose gel electrophoresis and flow cytometry (FCM) analyses to determine the apoptosis status of breast cancer MCF-7 cells, cervicalcancer HeLa cells and ovarian cancer HO8910 cells. Our results showed that the fungal taxol inhibited the growth of MCF-7, HeLa and HO8910 cells in a dose-and time-dependent manner. IC50 values of fungal taxol for HeLa, MCF-7 and HO8910 cells were 0.1-1.0 ?g/ml, 0.001-0.01 ?g/ml and 0.01- 0.1 ?g/ml, respectively. The fungal taxol induced these tumor cells to undergo apoptosis with typical apoptotic characteristics, including morphological changes for chromatin condensation, chromatin crescent formation, nucleus fragmentation, apoptotic body formation and G2/M cell cycle arrest. The fungal taxol at the 0.01-1.0 ?g/ ml had significant effects of inducing apoptosis between 24-48 h, which was the same as that of taxol extracted from yews. This study offers important information and a new resource for the production of an important anticancer drug by endofungus fermentation. PMID:25640339

Cancer etiology is influenced by alterations in protein synthesis that are not fully understood. In this study, we took a novel approach to investigate the role of the eukaryotic translation initiation factor eIF5A in human cervicalcancers, where it is widely overexpressed. eIF5A contains the distinctive amino acid hypusine, which is formed by a posttranslational modification event requiring deoxyhypusine hydroxylase (DOHH), an enzyme that can be inhibited by the drugs ciclopirox and deferiprone. We found that proliferation of cervicalcancercells can be blocked by DOHH inhibition with either of these pharmacologic agents, as well as by RNA interference-mediated silencing of eIF5A, DOHH, or another enzyme in the hypusine pathway. Proteomic and RNA analyses in HeLa cervicalcancercells identified two groups of proteins in addition to eIF5A that were coordinately affected by ciclopirox and deferiprone. Group 1 proteins (Hsp27, NM23, and DJ-1) were downregulated at the translational level, whereas group 2 proteins (TrpRS and PRDX2) were upregulated at the mRNA level. Further investigations confirmed that eIF5A and DOHH are required for Hsp27 expression in cervicalcancercells and for regulation of its key target I?B and hence NF-?B. Our results argue that mature eIF5A controls a translational network of cancer-driving genes, termed the eIF5A regulon, at the levels of mRNA abundance and translation. In coordinating cell proliferation, the eIF5A regulon can be modulated by drugs such as ciclopirox or deferiprone, which might be repositioned to control cancercell growth. PMID:24220243

Deregulated expression of high-risk human papillomavirus oncogenes (E6 and E7) is a pivotal event for pathogenesis and progression in cervicalcancer. Both viral oncogenes are therefore regarded as ideal therapeutic targets. In the hope of developing a gene-specific therapy for HPV-related cancer, we established CRISPR/Cas9 targeting promoter of HPV 16 E6/E7 and targeting E6, E7 transcript, transduced the CRISPR/Cas9 into cervical HPV-16-positive cell line SiHa. The results showed that CRISPR/Cas9 targeting promoter, as well as targeting E6 and E7 resulted in accumulation of p53 and p21 protein, and consequently remarkably reduced the abilities of proliferation of cervicalcancercells in vitro. Then we inoculated subcutaneously cells into nude mice to establish the transplanted tumor animal models, and found dramatically inhibited tumorigenesis and growth of mice incubated by cells with CRISPR/Cas9 targeting (promoter+E6+E7)-transcript. Our results may provide evidence for application of CRISPR/Cas9 targeting HR-HPV key oncogenes, as a new treatment strategy, in cervical and other HPV-associated cancer therapy. PMID:25044113

The aim of the present study was to investigate the effects of aloe-emodin (AE) on the radiosensitivity and differentiation of HeLa human cervicalcancercells. Cell proliferation was assessed in the HeLa cervicalcancercell line by a methylthiazolyldiphenyl-tetrazolium bromide assay. Radiosensitivity was determined by a colony?forming assay. Flow cytometry was used for analysis of cell cycle distribution and apoptosis. The expression of ?-H2AX and cyclin B was assessed by western blotting. Alkaline phosphatase (ALP) activity was measured by an ALP activity kit. It was demonstrated that AE inhibited the proliferation of HeLa cells in a concentration- and time-dependent manner, induced G2/M and S phase cell cycle arrest and enhanced the radiosensitivity of HeLa cells. The combination of AE and radiation induced apoptosis, upregulated cyclin B and ?-H2AX expression and further improved ALP activity compared with treatment with AE or radiation alone. AE enhanced the radiosensitivity of HeLa human cervicalcancercells in vitro, inhibited the proliferation of HeLa cells, induced G2/M phase cell cycle arrest and, in combination with radiation, induced the apoptosis and improved the differentiation of HeLa cells. PMID:24920336

Honey is reported to contain various compounds such as phenols, vitamins and antioxidants. The present study investigates the anticancer potential of Tualang honey (Agromas) (TH) in human breast (MCF-7 and MDA-MB-231) and cervical (HeLa) cancercell lines; as well as in the normal breast epithelial cell line, MCF-10A. The cells were treated with increasing doses of TH (1-10%) for up to 72 h. Increase in lactate dehydrogenase (LDH) leakage from the cell membranes indicates that TH is cytotoxic to all three cancercells with effective concentrations (EC(50)) of 2.4-2.8%. TH is however, not cytotoxic to the MCF-10A cells. Reactivity with annexin V fluorescence antibody and propidium iodide as analysed by flow cytometry and fluorescence microscopy shows that apoptosis occurred in these cancercells. TH also reduced the mitochondrial membrane potential (??(m)) in the cancercell lines after 24h of treatment. The activation of caspase-3/7 and -9 was observed in all TH-treated cancercells indicating the involvement of mitochondrial apoptotic pathway. This study shows that TH has significant anticancer activity against human breast and cervicalcancercell lines. PMID:21167897

Aim:The aim of this study was to investigate the effects of aloe-emodin, a natural compound from the root and rhizome of Rheum palmatum, on the growth of human cervicalcancercells, HeLa.Methods:HeLa cells were treated with various concentrations of aloe-emodin for 1-5 d, and cell growth was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay. The long-term growth effect was

Time trends in the incidence of cervical adenocarcinoma and adenosquamous cell carcinomas during the period 1973-1991 were examined using data provided by 60 population-based cancer registries from 32 defined populations in 25 countries. Three components of the incidence trend were studied: age, calendar period of diagnosis and birth cohort. Cumulative incidence rates per 1,000 for 2 groups with age ranges 25-49 and 50-74 years were calculated from the model that best described the incidence data. There was a significant increase in the cumulative incidence of cervical adenocarcinomas in women born in the mid-1930s and in successive cohorts thereafter in some populations in the United States (whites and Hispanic women), Australia, New Zealand (non-Maori), England, Scotland, Denmark, Slovenia, Slovakia and Japan (Osaka) and among Chinese women in Singapore, with a general decline in the incidence in women born in earlier periods. In Sweden and Slovenia there is a suggestion of an increasing trend in both age groups. A decrease in incidence in both age groups was apparent in Finland, France and Italy. There were no changes in incidence in 24 registries covering other European, Asian and black populations in the United States. Part of the increase may be attributable to an increasing prevalence of human papillomavirus infection, and part to improvements in screening. PMID:9466653

A case-control study of 480 patients with invasive cervicalcancer and 797 population controls, conducted in five geographic areas in the United States, included an evaluation of the relationship of several cigarette smoking variables to cervicalcancer risk. Although smoking was correlated with both age at first intercourse and number of sexual partners, a significant smoking-related risk persisted for squamous cell carcinoma after adjustment for these factors (relative risk, 1.5). Twofold excess risks were seen for those smoking 40 or more cigarettes per day and those smoking for 40 or more years. Increased risks, however, were observed only among recent and continuous smokers. In contrast to squamous cellcancer, no relationship was observed between smoking and risk of adenocarcinoma or adenosquamous carcinoma. These results suggest a causal relationship between cigarette smoking and invasive squamous cellcervicalcancer, perhaps through a late-stage or promotional event, although the mechanisms of action require further elucidation.

The concept of Ayurvedic expert guided drug discovery and development is defined and put to test systematically for the first time in literature. Western Science has explored only ~5% of the approximately 25,000 species of higher plants for drug leads. The ancient medical science of Ayurveda has however employed a much larger spectrum of plants for clinical treatment. Clerodendrum viscosum (CV), a commonly growing weed in the Indian subcontinent has been employed by S. Nirmalananda (Ayurvedic expert) for the treatment of cervicalcancer. Here we isolate and characterize a water extract fraction (Cv-AP) from the root of CV and evaluate its anticervical cancercell bioactivity. Our results indicate that Cv-AP possesses pro-apoptotic, anti-proliferative, and anti-migratory activity in a dose-dependent fashion against cervicalcancercell lines. In contrast, primary fibroblasts (control healthy cells), when exposed to similar concentrations of this extract, fail to undergo apoptosis and remain relatively unaffected. These findings suggest that Clerodendrum viscosum (CV) is a readily available source of components with potent anti-cancer activity and selective bioactivity against cervicalcancercells. The major component in CV-AP was identified as a glycoprotein via SDS Page and Concanavalin-A binding studies. This study serves to illustrate that systematic collaboration with Ayurveda is a practical and powerful strategy in drug discovery and development. PMID:23387970

We used oligonucleotide microarrays to investigate gene expression changes associated with multi-step human papillomavirus type 16 (HPV16)-mediated carcinogenesis in vitro. Gene expression profiles in 4 early passage HPV16-immortalized human keratinocyte (HKc) lines derived from different donors were compared with their corresponding 4 late-passage, differentiation-resistant cell lines, and to 4 pools of normal HKc, each composed of 3 individual HKc strains, on Agilent 22 k human oligonucleotide microarrays. The resulting data were analyzed using a modified T-test coded in R to obtain lists of differentially expressed genes. Gene expression changes identified in this model system were then compared with gene expression changes described in published studies of cervical intraepithelial neoplasia (CIN) and cervicalcancer. Common genes in these lists were further studied by cluster analysis. Genes whose expression changed in the same direction as in CIN or cervicalcancer (concordant) at late stages of HPV16-mediated transformation in vitro formed one major cluster, while those that changed in the opposite direction (discordant) formed a second major cluster. Further annotation found that many discordant expression changes involved gene products with an extracellular localization. Two novel genes were selected for further study: overexpression of SIX1 and GDF15, observed during in vitro progression in our model system, was confirmed in tissue arrays of cervicalcancer. These micro-array-based studies show that our in vitro model system reflects many cellular and molecular alterations characteristic of cervicalcancer, and identified SIX1 and GDF15 as 2 novel potential bio-markers of cervicalcancer progression. PMID:18398830

We have shown that in up to half of the patients with metastatic breast cancer (MBC), higher numbers of circulating tumour cells (CTCs) are present in the central venous blood (CVB) compared to the peripheral venous blood (PVB), suggesting that the lungs might retain a substantial number of CTCs. Here we report the presence of tumour cell emboli (TCE) in the microvasculature of the lungs in three out of eight patients with MBC and one patient with metastatic cervical carcinoma who had markedly elevated numbers of CTCs in the blood. All these patients suffered from symptomatic dyspnoea not easily attributable to other causes. No TCE were observed in five patients with MBC and elevated CTC counts and three patients with MBC who had low CTC counts (<5/7.5?ml). To investigate whether CTCs derived from CVB or PVB exhibit different transcriptional characteristics that might explain selective CTC retention, paired CTC samples from CVB and PVB of 12 patients with advanced breast cancer were subjected to gene expression analysis of 105 genes. No significant differences in CTC gene expression were observed. Together, these data suggest that potentially clinically relevant CTC retention in the microvasculature of the lung can occur in a subset of patients with advanced metastatic breast and cervicalcancer, which seems to be transcriptionally non-selectively. PMID:25449778

Betulinic acid is a pentacyclic triterpenoid that exhibits anticancer functions in human cancercells. This study provides evidence that betulinic acid is highly effective against the human cervicalcancercell line HeLa by inducing dose- and time-dependent apoptosis. The apoptotic process was further investigated using a proteomics approach to reveal protein expression changes in HeLa cells following betulinic acid treatment. Proteomic analysis revealed that there were six up- and thirty down-regulated proteins in betulinic acid-induced HeLa cells, and these proteins were then subjected to functional pathway analysis using multiple analysis software. UDP-glucose 6-dehydrogenase, 6-phosphogluconate dehydrogenase decarboxylating, chain A Horf6-a novel human peroxidase enzyme that involved in redox process, was found to be down-regulated during the apoptosis process of the oxidative stress response pathway. Consistent with our results at the protein level, an increase in intracellular reactive oxygen species was observed in betulinic acid-treated cells. The proteins glucose-regulated protein and cargo-selection protein TIP47, which are involved in the endoplasmic reticulum pathway, were up-regulated by betulinic acid treatment. Meanwhile, 14-3-3 family proteins, including 14-3-3? and 14-3-3?, were down-regulated in response to betulinic acid treatment, which is consistent with the decrease in expression of the target genes 14-3-3? and 14-3-3?. Furthermore, it was found that the antiapoptotic bcl-2 gene was down-regulated while the proapoptotic bax gene was up-regulated after betulinic acid treatment in HeLa cells. These results suggest that betulinic acid induces apoptosis of HeLa cells by triggering both the endoplasmic reticulum pathway and the ROS-mediated mitochondrial pathway. PMID:25148076

The p21-activated kinase 3 (PAK3) and the serum and glucocorticoid-induced kinase 2 (SGK2) have been previously proposed as essential kinases for human papillomavirus positive (HPV+) cervicalcancercell survival. This was established using a shRNA knockdown approach. To validate PAK3 and SGK2 as potential targets for HPV+ cervicalcancer therapy, the relationship between shRNA-induced phenotypes in HPV+ cervicalcancercells and PAK3 or SGK2 knockdown was carefully examined. We observed that the phenotypes of HPV+ cervicalcancercells induced by various PAK3 and SGK2 shRNAs could not be rescued by complement expression of respective cDNA constructs. A knockdown-deficient PAK3 shRNA with a single mismatch was sufficient to inhibit HeLa cell growth to a similar extent as wild-type PAK3 shRNA. The HPV+ cervicalcancercells were also susceptible to several non-human target shRNAs. The discrepancy between PAK3 and SGK2 shRNA-induced apoptosis and gene expression knockdown, as well as cell death stimulation, suggested that these shRNAs killed HeLa cells through different pathways that may not be target-specific. These data demonstrated that HPV+ cervicalcancercell death was not associated with RNAi-induced PAK3 and SGK2 knockdown but likely through off-target effects. PMID:25615606

Infection with high-risk human papillomaviruses is causally linked to cervical carcinogenesis. However, most lesions caused by high-risk HPV infections do not progress to cancer. Host cell mutations contribute to malignant progression but the molecular nature of such mutations is unknown. Based on a previous study that reported an association between liver kinase B1 (LKB1) tumor suppressor loss and poor outcome in cervicalcancer, we sought to determine the molecular basis for this observation. LKB1-negative cervical and lung cancercells were reconstituted with wild type or kinase defective LKB1 mutants and we examined the importance of LKB1 catalytic activity in known LKB1-regulated processes including inhibition of cell proliferation and elevated resistance to energy stress. Our studies revealed marked differences in the biological activities of two kinase defective LKB1 mutants in the various cell lines. Thus, our results suggest that LKB1 may be a cell-type specific tumor suppressor. PMID:24074562

High oncogenic risk human papillomaviruses (HPVs) are closely associated with cancer of the cervix. However, HPV infection alone may not be sufficient to cause cervicalcancer, and other factors or cofactors may have a cumulative effect on the risk of progression from cervical HPV infection to cancer. The present study investigates the cytosine?adenine (CA) repeat polymorphism in the P1 promoter region of the insulin?like growth factor?1 (IGF?1) gene among cervical precancerous and cancer patients and healthy control females. The association between these polymorphisms, tissue and blood serum levels of IGF?1, and cervicalcancer risk and progression is evaluated. The material for analysis consisted of blood cells and postoperative tissues from patients diagnosed with low?grade squamous intraepithelial lesions (L?SILs), high?grade squamous intraepithelial lesions (H?SILs) and invasive cervicalcancer (ICC). A polymerase chain reaction amplification and the sequencing of DNA were used for the identification of (CA)n repeats in the IGF?1 P1 region and detection of HPV DNA. The blood serum concentration of IGF was determined by enzyme?linked immunosorbent assay. The identification of the IGF?1 protein in the cervical tissues was performed by immunohistochemical analysis. The range of the length of the CA repeats in the study DNA was 11 to 21. However, the most common allele length and genotype in the control and study patients from serum and tissues was 19 CA repeats and a homozygous genotype of CA19/19. Statistically significant differences in the concentration of IGF?1 in the blood serum were observed between H?SILs and controls, only (p=0.047). However, the concentration of IGF?1 in the group of females with CA19/19, CA19<19 and CA19>19 was significantly higher in the group of patients with H?SIL (P=0.041) and ICC (P=0.048) in comparison with the control group. An association was detected between CA repeat length <19 and/or >19, IGF concentration in blood serum and tissues and the development of cervicalcancer. PMID:25384883

High oncogenic risk human papillomaviruses (HPVs) are closely associated with cancer of the cervix. However, HPV infection alone may not be sufficient to cause cervicalcancer, and other factors or cofactors may have a cumulative effect on the risk of progression from cervical HPV infection to cancer. The present study investigates the cytosine-adenine (CA) repeat polymorphism in the P1 promoter region of the insulin-like growth factor-1 (IGF-1) gene among cervical precancerous and cancer patients and healthy control females. The association between these polymorphisms, tissue and blood serum levels of IGF-1, and cervicalcancer risk and progression is evaluated. The material for analysis consisted of blood cells and postoperative tissues from patients diagnosed with low-grade squamous intraepithelial lesions (L-SILs), high-grade squamous intraepithelial lesions (H-SILs) and invasive cervicalcancer (ICC). A polymerase chain reaction amplification and the sequencing of DNA were used for the identification of (CA)n repeats in the IGF-1 P1 region and detection of HPV DNA. The blood serum concentration of IGF was determined by enzyme-linked immunosorbent assay. The identification of the IGF-1 protein in the cervical tissues was performed by immunohistochemical analysis. The range of the length of the CA repeats in the study DNA was 11 to 21. However, the most common allele length and genotype in the control and study patients from serum and tissues was 19 CA repeats and a homozygous genotype of CA19/19. Statistically significant differences in the concentration of IGF-1 in the blood serum were observed between H-SILs and controls, only (p=0.047). However, the concentration of IGF-1 in the group of females with CA19/19, CA19<19 and CA19>19 was significantly higher in the group of patients with H-SIL (P=0.041) and ICC (P=0.048) in comparison with the control group. An association was detected between CA repeat length <19 and/or >19, IGF concentration in blood serum and tissues and the development of cervicalcancer. PMID:25384883

In January, CRCHD joins the nation in raising awareness for Cervical Health and CervicalCancer Disparities. This month we share a special focus on NCI/CRCHD research programs that are trying to reduce cervicalcancer disparities in underserved communities and the people who are spreading the word about the importance of early detection.

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for cervicalcancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

High-risk human papillomavirus (HR-HPV) infections are among the most important factors for cervical carcinogenesis. However, whether patients infected with HR-HPV eventually develop a malignant tumor, largely depends on epithelial-mesenchymal transition (EMT), which plays an extraordinary role in the process of carcinogenesis and metastasis. Therefore, we evaluated the protein levels of EMT-related genes in normal cervical squamous epithelium, cervical intraepithelial neoplasia (CIN), and cervical squamous cell carcinoma (SCC) by tissue microarray and immunohistochemical staining. By comparing the expression of EMT-related proteins in 31 cases of cervical tumors and tumor adjacent tissues and exploring the relationship between HPV16 oncogenes and EMT in vitro, we found that Twist2 protein levels were significantly higher in CIN and cervicalcancer than in normal cervical squamous epithelial samples (p<0.01 and p<0.001, respectively). This finding corresponded with the decreased expression of E-cadherin in cervicalcancer. The difference in the expression of Twist2 and E-cadherin between 31 cases of cervical tumors and tumor adjacent tissues was statistically significant (p<0.01). HPV16 oncogenes were able to induce morphological alterations in the SiHa cell line, upregulate the expression of Twist2 and vimentin, downregulate E-cadherin in vitro, and exert an effect on invasion. Thus, joint detection of Twist2 and E-cadherin expression can help evaluate and provide greater insight into cervical carcinogenesis and progression. PMID:25420506

Small-molecule inhibitors targeted MAPK have been wildly used for some cancer therapeutics as a biologically viable model, but no one has been used for cervical caner. ERK1/2, one of MAPK kinases, is expressed high in cervicalcancer tissue. The aim of the present study was to evaluate the effects of ERK1/2 inhibitor U0126 on proliferation and apoptosis of cervicalcancercells and appraise the correlated mechanism of the effects. In this study, the cell proliferation of Hela and C33A cervicalcancercells was tested by Cell Counting Kit-8 (CCK8) assay and cell counting after treated with ERK1/2 inhibitor U0126. The cell cycle and apoptosis were evaluated by flow cytometry (FCM). The protein levels of ERK1/2 and c-Fos and c-Jun were detected by Western blot. The results indicated that after down-regulating ERK1/2 proteins with the inhibitor U0126, Hela and C33A cells proliferation was inhibited, cell apoptosis was promoted, the proportions of G0/G1 stage in cell cycle increased, and G2/M stages decreased. After down-regulating ERK1/2 proteins of Hela and C33A cells, the expression levels of p-c-Fos protein decreased, while p-c-Jun protein increased. The results of this study indicated that ERK1/2 may promote the development of cervicalcancercells, suggesting ERK1/2 inhibitor may be used as an effective target for cervicalcancer therapies working for. It might inhibit cervicalcancercells growth via regulating the transcription factors expression of c-Fos and c-Jun. PMID:25647783

Objective IL-17A plays an important role in many inflammatory diseases and cancers. We aimed to examine the effect of IL-17A on the invasion of cervicalcancercells and study its related mechanisms. Methods Wound healing and matrigel transwell assays were used to examine the effect of IL-17A on cervicalcancercell migration and invasion by a panel of cervicalcancercell lines. The levels of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) were investigated using western blotting. The activity of p38 and nuclear factor-kappa B (NF-?B) signal pathway was detected too. Results Here, we showed that IL-17A could promote the migration and invasion of cervicalcancercells. Further molecular analysis showed that IL-17A could up-regulate the expressions and activities of MMP2 and MMP9, and down-regulate the expressions of TIMP-1 and TIMP-2. Furthermore, IL-17A also activates p38 signal pathway and increased p50 and p65 nuclear expression. In addition, treatment of cervicalcancercells with the pharmacological p38/NF-?B signal pathway inhibitors, SB203580 and PDTC, potently restored the roles of invasion and upregulation of MMPs induced by IL-17A. Conclusion IL-17A could promote the migration and invasion of cervicalcancercell via up-regulating MMP2 and MMP9 expression, and down-regulating TIMP-1 and TIMP-2 expression via p38/NF-?B signal pathway. IL-17A may be a potential target to improve the prognosis for patients with cervicalcancer. PMID:25250801

background Infection with human papilloma virus (HPV) is the main cause of cervicalcancer, but the risk associated with the various HPV types has not been adequately assessed. methods We pooled data from 11 case-control studies from nine countries involving 1918 wom- en with histologically confirmed squamous-cellcervicalcancer and 1928 control wom- en. A common protocol and questionnaire were

The aim of the present study was to examine Cdc42 expression in cervicalcancer and explore its effects on invasion and migration capability of cervicalcancercells. Immunohistochemistry was used to detect Cdc42 expression in normal cervical tissues as well as CIN I or below, CIN II or above, and cervicalcancer tissues. Western blot analysis was used to explore Cdc42 expression in normal cervicalcell line Crl-2614 and cervicalcancercell line HeLa. Plasmids of constitutively active Cdc42 (Cdc42 CA), wild-type Cdc42 (Cdc42 WT) and dominant negative Cdc42 (Cdc42 DN) were transfected, respectively, into HeLa cells to investigate the impacts of Cdc42 on migration and invasion of cervicalcancercells using Transwell and on cytoskeleton microfilaments using confocal microscopy after immunofluorescence staining. Cdc42 expression was gradually increased in the order of cervical tissues with CIN I or below, CIN II or above and cancer, showing significant difference (P<0.05), and was significantly higher in HeLa cells than in Crl-2614 cells (P<0.05). Migration ability of HeLa cells transfected with Cdc42 CA was significantly higher than that of non-transfected, as well as Cdc42 WT- or Cdc42 DN-transfected HeLa cells (P<0.05). Overexpression of Cdc42 CA can promote filopodia formation in HeLa cells. We concluded that Cdc42 overexpression significantly improved the ability of cervicalcancercells to migrate possibly due to improved pseudopodia formation. PMID:25394485

Background Sun ginseng (SG), a specific formulation of quality-controlled red ginseng, contains approximately equal amounts of three major ginsenosides (RK1, Rg3, and Rg5), which reportedly has antitumor-promoting activities in animal models. Methods MTT assay was used to assess whether SG can potentiate the anticancer activity of epirubicin or paclitaxel in human cervical adenocarcinoma HeLa cells, human colon cancer SW111C cells, and SW480 cells; apoptosis status was analyzed by annexin V-FITC and PI and analyzed by flow cytometry; and apoptosis pathway was studied by analysis of caspase-3, -8, and -9 activation, mitochondrial accumulation of Bax and Bak, and cytochrome c release. Results SG remarkably enhances cancercell death induced by epirubicin or paclitaxel in human cervical adenocarcinoma HeLa cells, human colon cancer SW111C cells, and SW480 cells. Results of the mechanism study highlighted the cooperation between SG and epirubicin or paclitaxel in activating caspase-3 and -9 but not caspase-8. Moreover, SG significantly increased the mitochondrial accumulation of both Bax and Bak triggered by epirubicin or paclitaxel as well as the subsequent release of cytochrome c in the targeted cells. Conclusion SG significantly potentiated the anticancer activities of epirubicin and paclitaxel in a synergistic manner. These effects were associated with the increased mitochondrial accumulation of both Bax and Bak that led to an enhanced cytochrome c release, caspase-9/-3 activation, and apoptosis. Treating cancercells by combining epirubicin and paclitaxel with SG may prove to be a novel strategy for enhancing the efficacy of the two drug types.

This study was aimed at identifying the signalling pathways involved in the activation of volume-regulatory mechanisms of human cervicalcancercells. Osmotic swelling of human cervicalcancercells induced a substantial increase in intracellular Ca2+ ([Ca2+]i) by the activation of Ca2+ entry across the cell membrane, as well as Ca2+ release from intracellular stores. This Ca2+ signalling was critical for the normal regulatory volume decrease (RVD) response. The activation of swelling-activated ion and taurine transport was significantly inhibited by tyrosine kinase inhibitors (genistein and tyrphostin AG 1478) and potentiated by the tyrosine phosphatase inhibitor Na3VO4. However, the Src family of tyrosine kinases was not involved in regulation of the swelling-activated Cl? channel. Cell swelling triggered mitogen-activated protein (MAP) kinase cascades leading to the activation of extracellular signal-regulated kinase 1 and 2 (ERK1/ERK2) and p38 kinase. The volume-responsive ERK1/ERK2 signalling pathway linked with the activation of K+ and Cl? channels, and taurine transport. However, the volume-regulatory mechanism was independent of the activation of p38 MAP kinase. The phosphorylated ERK1/ERK2 expression following a hypotonic shock was up-regulated by protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) and down-regulated by PKC inhibitor staurosporine. The response of ERK activation to hypotonicity also required Ca2+ entry and depended on tyrosine kinase and mitogen-activated/ERK-activating kinase (MEK) activity. Considering the results overall, osmotic swelling promotes the activation of tyrosine kinase and ERK1/ERK2 and raises intracellular Ca2+, all of which play a crucial role in the volume-regulatory mechanism of human cervicalcancercells. PMID:11731569

Carbon nanotubes are capable of penetrating the cell membrane and are widely considered as potential carriers for gene or drug delivery. Because the C-C and C=C bonds in carbon nanotubes are nonpolar, functionalization is required for carbon nanotubes to interact with genes or drugs as well as to improve their biocompatibility. In this study, polyethylenimine (PEI)-functionalized single-wall (PEI-NH-SWNTs) and multiwall carbon nanotubes (PEI-NH-MWNTs) were produced by direct amination method. PEI functionalization increased the positive charge on the surface of SWNTs and MWNTs, allowing carbon nanotubes to interact electrostatically with the negatively charged small interfering RNAs (siRNAs) and to serve as nonviral gene delivery reagents. PEI-NH-MWNTs and PEI-NH-SWNTs had a better solubility in water than pristine carbon nanotubes, and further removal of large aggregates by centrifugation produced a stable suspension of reduced particle size and improved homogeneity and dispersity. The amount of grafted PEI estimated by thermogravimetric analysis was 5.08% (w/w) and 5.28% (w/w) for PEI-NH-SWNTs and PEI-NH-MWNTs, respectively. For the assessment of cytotoxicity, various concentrations of PEI-NH-SWNTs and PEI-NH-MWNTs were incubated with human cervicalcancercells, HeLa-S3, for 48 h. PEI-NH-SWNTs and PEI-NH-MWNTs induced cell deaths in a dose-dependent manner but were less cytotoxic compared to pure PEI. As determined by electrophoretic mobility shift assay, siRNAs directed against glyceraldehyde-3-phosphate dehydrogenase (siGAPDH) were completely associated with PEI-NH-SWNTs or PEI-NH-MWNTs at a PEI-NH-SWNT/siGAPDH or PEI-NH-MWNT/siGAPDH mass ratio of 80:1 or 160:1, respectively. Furthermore, PEI-NH-SWNTs and PEI-NH-MWNTs successfully delivered siGAPDH into HeLa-S3 cells at PEI-NH-SWNT/siGAPDH and PEI-NH-MWNT/siGAPDH mass ratios of 1:1 to 20:1, resulting in suppression of the mRNA level of GAPDH to an extent similar to that of DharmaFECT, a common transfection reagent for siRNAs. Our results indicate that the PEI-NH-SWNTs and PEI-NH-MWNTs produced in this study are capable of delivering siRNAs into HeLa-S3 cells to suppress gene expression and may therefore be considered as novel nonviral gene delivery reagents. PMID:23742156

Cervicalcancer is the second most common female malignancy in Serbia, after breast cancer, with 1089 new registered cases and an age-standardized incidence rate of 27.2 per 100,000 women in 2002. It is the fourth leading cause of cancer death with 452 deaths and an age-standardized death rate of 7.2 per 100,000 women. Compared with other European countries, the incidence of cervicalcancer in Central Serbia is the highest. Regional differences in incidence are pronounced in Serbia with the lowest age-standardized incidence rate (16.6 per 100,000 women) registered in the Macvanski region and the highest in eastern Serbia and the region of Belgrade where the rates are double at 32.5-38.1 per 100,000 women. Cervicalcancer prevention in Serbia has relied on opportunistic screening that is characterized by high coverage in younger and low coverage in middle-aged and older women. Screening of selected groups of women employed in large companies is performed annually by many regional hospitals but this approach has little effect on morbidity and mortality. Recently, the Ministry of Health nominated an Expert Group to develop and implement a national cervicalcancer screening program. A number of pilot projects have been undertaken with the results used for development of a national programme for cervicalcancer screening. This is expected to be finalized in 2007, and launched over a 3-years period in order to cover all women aged 25-64 in entire Serbia. PMID:17598502

Variation in human major histocompatibility genes may influence the risk of squamous cellcervicalcancer (SCC) by altering the efficiency of the T cell mediated immune response to HPV antigens. We used high resolution methods to genotype HLA Class I (A, B, and Cw) and Class II (DRB1 and DQB1) loci in 544 women with SCC and 542 controls. Recognizing that HLA molecules are co-dominantly expressed, we focused on co-occurring alleles. Among 137 allele combinations present at >5% in the case or control groups, 36 were significantly associated with SCC risk. All but one of the 30 combinations that increased risk included DQB1*0301, and 23 included subsets of A*0201-B*4402-Cw*0501-DRB1*0401-DQB1*0301. Another combination, B*4402-DRB1*1101-DQB1*0301, conferred a strong risk of SCC (OR 10.0, 95% CI 3.0-33.3). Among the 6 combinations that conferred a decreased risk of SCC, 4 included Cw*0701 or DQB1*02. Most multilocus results were similar for SCC that contained HPV16; a notable exception was A*0101-B*0801-Cw*0701-DRB1*0301-DQB1*0201 and its subsets, which were associated with HPV16+ SCC (OR 0.5, 95% CI 0.3-0.9). The main multilocus associations were replicated in studies of cervical adenocarcinoma and vulvar cancer. These data confirm that T helper and cytotoxic T cell responses are both important cofactors with HPV in cervicalcancer etiology, and indicate that co-occurring HLA alleles across loci appear to be more important than individual alleles. Thus, certain co-occurring alleles may be markers of disease risk that have clinical value as biomarkers for targeted screening or development of new therapies. PMID:18451182

The aim of this study was to describe the state of the art in cervicalcancer screening in Greece by presenting the two regionally organised screening programmes that currently operate in the country. Both programmes were initiated in 1991 and are partly funded by the European Union. The Ormylia screening programme covers the population of Halkidiki (Northern Greece), a predominantly

Objectives Hemoglobin (Hgb) is the main oxygen and carbon dioxide carrier in cells of erythroid lineage and is responsible for oxygen delivery to the respiring tissues of the body. However, Hgb is also expressed in nonerythroid cells. In the present study, the expression of Hgb in human uterine cervix carcinoma cells and its role in cervicalcancer were investigated. Methodology The expression level of Hgb in cervicalcancer tissues was assessed by quantitative reverse transcriptase-PCR (qRT-PCR). We applied multiple methods, such as RT-PCR, immunoblotting, and immunohistochemical analysis, to confirm Hgb expression in cervicalcancercells. The effects of ectopic expression of Hgb and Hgb mutants on oxidative stress and cell viability were investigated by cellular reactive oxygen species (ROS) analysis and lactate dehydrogenase (LDH) array, respectively. Both Annexin V staining assay by flow cytometry and caspase-3 activity assay were used, respectively, to evaluate cell apoptosis. Results qRT-PCR analysis showed that Hgb-?- (HBA1) and Hgb-?-globin (HBB) gene expression was significantly higher in cervical carcinoma than in normal cervical tissues, whereas the expression of hematopoietic transcription factors and erythrocyte specific marker genes was not increased. Immunostaining experiments confirmed the expression of Hgb in cancercells of the uterine cervix. Hgb mRNA and protein were also detected in the human cervical carcinoma cell lines SiHa and CaSki, and Hgb expression was up-regulated by hydrogen peroxide-induced oxidative stress. Importantly, ectopic expression of wild type HBA1/HBB or HBA1, rather than mutants HBA1H88R/HBBH93R unable to bind hemo, suppressed oxidative stress and improved cell viability. Conclusions The present findings show for the first time that Hgb is expressed in cervical carcinoma cells and may act as an antioxidant, attenuating oxidative stress-induced damage in cervicalcancercells. These data provide a significant impact not only in globin biology but also in understanding of cervicalcancer pathogenesis associated with oxidative stress. PMID:23349856

The activation of signal transducer and activator of transcription 3 (Stat3) has been implicated in the oncogenesis of cancer and is regarded as a novel target for cancer therapy. Stat3 is classified as a proto-oncogene, because an activated form of Stat3 can mediate oncogenic transformation in cultured cells and tumour formation in nude mice. The constitutive activation of Stat3 has been frequently detected in various types of human cancers. However, the constitutive activation of Stat3 in endometrial and cervicalcancers has not been studied. We examined tyrosine phosphorylation of Stat3 (activated form of Stat3) in multiple endometrial and cervicalcancer tissues using tissue microarray slides as well as cancercell lines to explore the possible activation of Stat3. Our results indicated that elevated phosphorylation of Stat3 was detected in cervical and endometrial cancercell lines. Our results also showed that elevated levels of phosphorylation of Stat3 protein were detected in the endometrial and cervicalcancer specimens. This is the first study to demonstrate that Stat3 is activated in human endometrial and cervicalcancer tissues. Immunohistochemical staining showed that activated Stat3 is associated with increased expression of downstream antiapoptotic genes, Bcl-xL, survivin, and Mcl-1 in these tissues. Expression of a dominant-negative Stat3 mutant using adenovirus-mediated gene transfer inhibited cell growth and induced apoptosis in HeLa and SiHa cervicalcancercell lines expressing elevated levels of Stat3 phosphorylation. Further, a JAK/Stat3 small molecular inhibitor, JSI-124, induced apoptosis more selectively in HeLa and SiHa cancercell lines than Ishikawa cell line without elevated levels of Stat3 phosphorylation. These results indicate that Stat3 is activated in human endometrial and cervicalcancers and the inhibition of constitutive Stat3 signaling may be an effective target for cancer intervention in these two cancers. PMID:17311011

Fluorescent molecular probes offer a potential for early cancer detection. Indocyanine green (ICG) is an FDAapproved near-infrared (NIR) fluorescent dye used in ophthalmic angiography and assessment of cardiac and hepatic functions. However, clinical applications of ICG remain very limited due to its rapid clearance from vascular circulation, unstable optical properties, non-specific interactions with plasma proteins, and inability for localized targeting. To overcome these limitations, we have encapsulated ICG within nanoconstructs composed of poly(allylamine) hydrochloride and disodium hydrogen phosphate salt. To understand the effects of coating materials on the cellular uptake of the nanocapsules, we have measured the uptake of ICG-loaded nanocapsules (ICG-NCs) with various coating materials by HeLa cancerouscervical epithelial cells in-vitro. Results of this study provide important information for the choice of appropriate coating materials that will result in maximal uptake of ICG-NCs in optical and phototherapy of cancerous tissue.

Cervicalcancer is the third most common cancer among women worldwide and is responsible for 275.000 deaths each year. The development of cervicalcancer has been linked to cell cycle disturbances caused by persistent expression of the high- risk HPV oncoproteins (E5, E6 and E7), which modulate the expression of host genes and cellular microRNAs. An estimated 5 million women throughout the world are currently infected by HPV and several of them will develop invasive cervicalcancer. Despite failures in conventional screening tests, approved therapies have no direct effect on HPV infection. Therefore, effective therapy for cervicalcancer is still urgently needed, particularly in developing countries where more than 85% of fatal cases occur. In this way, in this paper we review the current molecular targeted therapies which are being explored and may have a significant impact on the treatment of HPV- related cervical dysplasia and carcinoma. PMID:25479546

The development of robotic technology has facilitated the application of minimally invasive techniques for the treatment and evaluation of patients with early, advanced, and recurrent cervicalcancer. The application of robotic technology for selected patients with cervicalcancer and the data available in the literature are addressed in the present review paper. The robotic radical hysterectomy technique developed at the Mayo Clinic Arizona is presented with data comparing 27 patients who underwent the robotic procedure with 2 matched groups of patients treated by laparoscopic (N = 31), and laparotomic radical hysterectomy (N = 35). A few other studies confirmed the feasibility and safety of robotic radical hysterectomy and comparisons to either to the laparoscopic or open approach were discussed. Based on data from the literature, minimally invasive techniques including laparoscopy and robotics are preferable to laparotomy for patients requiring radical hysterectomy, with some advantages noted for robotics over laparoscopy. A prospective randomised trial is currently being perfomred under the auspices of the American Association of Gyneoclogic Laparoscopists comparing minimally invasive radical hysterectomy (laparoscopy or robotics) with laparotomy. For early cervicalcancer radical parametrectomy and fertility preserving trachelectomy have been performed using robotic technology and been shown to be feasible, safe, and easier to perform when compared to the laparoscopic approach. Similar benefits have been noted in the treatment of advanced and recurrent cervicalcancer where complex procedures such as extraperitoneal paraortic lymphadenectomy and pelvic exenteration have been required. Conclusion: Robotic technology better facilitates the surgical approach as compared to laparoscopy for technically challenging operations performed to treat primary, early or advanced, and recurrent cervicalcancer. Although patient advantages are similar or slightly improved with robotics, there are multiple advantages for surgeons. PMID:19108008

Evidences indicate that tumor development and progression towards a malignant phenotype depend not only on cancercells themselves, but are also deeply influenced by tumor stroma reactivity. The present study uses mesenchymal stem cells from normal human uterine cervix (hUCESCs), isolated by the minimally invasive method of routine Pap cervical smear, to study their effect on the three main cell types in a tumor: cancercells, fibroblasts and macrophages. Administration of hUCESCs-conditioned medium (CM) to a highly invasive breast cancer MDA-MB-231 cell line and to human breast tumors with high cell proliferation rates had the effect of reducing cell proliferation, modifying the cell cycle, inducing apoptosis, and decreasing invasion. In a xenograft mouse tumor model, hUCESCs-CM reduced tumor growth and increased overall survival. In cancer-associated fibroblasts, administration of hUCESCs-CM resulted in reduced cell proliferation, greater apoptosis and decreased invasion. In addition, hUCESCs-CM inhibited and reverted macrophage differentiation. The analysis of hUCESCs-CM (fresh and lyophilized) suggests that a complex paracrine signaling network could be implicated in the anti-tumor potential of hUCESCs. In light of their anti-tumor potential, the easy cell isolation method, and the fact that lyophilization of their CM conserves original properties make hUCESCs good candidates for experimental or clinical applications in anticancer therapy. PMID:25296979

Evidences indicate that tumor development and progression towards a malignant phenotype depend not only on cancercells themselves, but are also deeply influenced by tumor stroma reactivity. The present study uses mesenchymal stem cells from normal human uterine cervix (hUCESCs), isolated by the minimally invasive method of routine Pap cervical smear, to study their effect on the three main cell types in a tumor: cancercells, fibroblasts and macrophages. Administration of hUCESCs-conditioned medium (CM) to a highly invasive breast cancer MDA-MB-231 cell line and to human breast tumors with high cell proliferation rates had the effect of reducing cell proliferation, modifying the cell cycle, inducing apoptosis, and decreasing invasion. In a xenograft mouse tumor model, hUCESCs-CM reduced tumor growth and increased overall survival. In cancer-associated fibroblasts, administration of hUCESCs-CM resulted in reduced cell proliferation, greater apoptosis and decreased invasion. In addition, hUCESCs-CM inhibited and reverted macrophage differentiation. The analysis of hUCESCs-CM (fresh and lyophilized) suggests that a complex paracrine signaling network could be implicated in the anti-tumor potential of hUCESCs. In light of their anti-tumor potential, the easy cell isolation method, and the fact that lyophilization of their CM conserves original properties make hUCESCs good candidates for experimental or clinical applications in anticancer therapy. PMID:25296979

Latex of Euphorbia antiquorum (EA) has inhibitory effects on several different cancercell lines. However, the molecular mechanism of EA inhibitory effects on human cervicalcancer HeLa cell growth has not been explored. EA induced apoptosis, which was characterized by morphological change, DNA fragmentation, increased sub-G1 population, and alterations in levels of apoptosis-associated proteins. Treatment with EA increased cell death

Although cervicalcancer is only the fifth leading cause of cancer deaths in women globally, it remains the leading cause of cancer deaths among women in developing countries. The approach to cervicalcancer prevention used in developed countries has failed in most of the world because widespread Pap smear screening and the evaluation by specialists of women who screen positive

Foxp3(+) CD4(+)CD25(+) regulatory T (Treg) cells and immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) play an important role in immunoregulation. Accumulating evidence shows that IDO and Treg cells have potent regulatory properties for immune escape in cancer. To evaluate the expression of IDO and the localization of Foxp3(+) Treg cells in the development and progression of uterine cervicalcancer, IDO expression and Foxp3(+) Treg cells in the primary and metastatic lesions were studied using immunohistochemistry. IDO expression in tumor cells appeared in cervical intraepithelial neoplasia (CIN)-3 of the uterine cervix and marked expression in microinvasive cancercells was observed. Interestingly, IDO expression in invasive cancer was confined to the cancercells at the invasive front. Moreover, antigen-presenting cells (APC) at the invasive front in primary and metastatic lesions were also expressing IDO. Stromal Foxp3(+) Treg cells appeared in CIN-3 and increased in microinvasive and invasive cancer. Intraepithelial Foxp3(+) Treg cells were restricted within microinvasive and invasive cancer. No significant differences in the proportion of Foxp3(+)/CD4(+) in the stroma or epithelium, or between non-metastatic and metastatic invasive cancers, were observed in primary lesions of cervicalcancer, while there was a significant increase (P < 0.005) in the proportion of Foxp3(+)/CD4(+) in metastatic lymph nodes compared with non-metastatic lymph nodes. Some of the Foxp3(+) Treg cells in metastatic lymph nodes contacted the IDO(+) APC. IDO expression at the invasive front of cancercells and APC, and the localization of Foxp3(+) Treg cells in front of cancer tissues, may create a network between IDO and Treg for the induction of immune escape. PMID:17433037

To improve our understanding of cervical adenocarcinoma (AD) and evaluate the clinical and pathological variables affecting its prognosis, we retrospectively reviewed the medical records of 455 patients with cervicalcancer [International Federation of Gynecology and Obstetrics stage I/II; 91 cases with AD and 364 with squamous cell carcinoma (SCC)] who underwent surgery at our hospital between January, 1995 and August, 2012 and compared the characteristics and prognoses between AD and SCC cases, including age, clinical stage, histological type, lymph node metastasis, lymphovascular space invasion (LVSI), cervical stromal invasion, parametrial invasion, vaginal invasion, corpus invasion, ovarian metastasis and tumor diameter. We used Cox regression analysis to determine independent prognostic factors. AD was found to have a significantly poorer prognosis in all the patients (P=0.001), stage I patients (P=0.001) and stage IB patients (P<0.05). The prognosis did not differ in patients who did not require postoperative treatment; however, patients who received postoperative treatment exhibited a significantly poorer prognosis (P<0.05). Patients with AD who received postoperative irradiation alone had a significantly poorer prognosis (P<0.05). The multivariate analysis identified LVSI (P=0.008), stromal invasion (P=0.024) and ovarian metastasis (P=0.032) as independent predictors of shorter survival. AD was associated with a worse prognosis compared to SCC in patients with stage IB disease, particularly in those who required postoperative treatment. Such patients may benefit from individualized postoperative treatments that differ from those applied for SCC. PMID:24940487

Inflammation is known to be closely associated with the development of cancer. The study was launched in human cervicalcancer HeLa cells to investigate the antitumor and anti-inflammatory effects of P2, a marine polypeptide fraction from an important fishery resource Arca subcrenata. The basic research showed that P2 could suppress the production of nitric oxide in LPS-induced RAW264.7 macrophage cells as well as the secretion of inflammatory cytokines IL-6 and TNF-? in human cervicalcancer HeLa cells. For the molecular mechanisms, P2 was shown to downregulate the gene expression of proinflammatory cytokines IL-6 and IL-8 and to inhibit the COX-2 and iNOS-related pathways in HeLa cells. In consequence, P2 might inhibit tumor development by blocking the interaction between tumor microenvironment and proinflammatory mediators. All findings indicate that P2 possesses the potential to be developed as a novel agent for cancer therapy. PMID:24683359

Background In Greenland, the incidence of cervicalcancer caused by human papillomavirus (HPV) is 25 per 100,000 women; 2.5 times the Danish rate. In Greenland, the disease is most frequent among women aged 30–40. Systematic screening can identify women with cervicalcell changes, which if untreated may cause cervicalcancer. In 2007, less than 40% of eligible women in Greenland participated in screening. Objective To examine Greenlandic women's perception of disease, their understanding of the connection between HPV and cervicalcancer, and the knowledge that they deem necessary to decide whether to participate in cervicalcancer screening. Study design The methods used to perform this research were 2 focus-group interviews with 5 Danish-speaking women and 2 individual interviews with Greenlandic-speaking women. The analysis involved a phenomenological-hermeneutic approach with 3 levels of analysis: naive reading, structural analysis and critical interpretation. Results These revealed that women were unprepared for screening results showing cervicalcell changes, since they had no symptoms. When diagnosed, participants believed that they had early-stage cancer, leading to feelings of vulnerability and an increased need to care for themselves. Later on, an understanding of HPV as the basis for diagnosis and the realization that disease might not be accompanied by symptoms developed. The outcome for participants was a life experience, which they used to encourage others to participate in screening and to suggest ways that information about screening and HPV might reach a wider Greenlandic population. Conclusion Women living through the process of cervical disease, treatment and follow-up develop knowledge about HPV, cervicalcell changes, cervical disease and their connection, which, if used to inform cervical screening programmes, will improve the quality of information about HPV, cervicalcancer and screening participation. This includes that verbal and written information given at the point of screening and diagnosis needs to be complemented by visual imagery. PMID:23984277

early detection and treatment. However, cur- rent detection techniques, such as Pap smear and colposcopy intraepithelial lesion (SIL). Currently, a Pap smear is used to #12;screen for cervicalcancer (Kurman et al., 1994). In a Pap test, a large number of cells obtained by scraping the cervical epithelium are smeared

Taxol (paclitaxel) is a potent anticancer drug that has been found to be effective against several tumor types, including cervicalcancer. However, the exact mechanism underlying the antitumor effects of paclitaxel is poorly understood. Here, paclitaxel induced the apoptosis of cervicalcancer HeLa cells and correlated with the enhanced activation of caspase-3 and TAp73, which was strongly inhibited by TAp73? small interfering RNA (siRNA). In wild-type activating transcription factor 3 (ATF3)–overexpressed cells, paclitaxel enhanced apoptosis through increased ? and ? isoform expression of TAp73; however, these events were attenuated in cells containing inactive COOH-terminal–deleted ATF3 [ATF3(?C)] or ATF3 siRNA. In contrast, paclitaxel-induced ATF3 expression did not change in TAp73? -overexpressed or TAp73? siRNA–cotransfected cells. Furthermore, paclitaxel-induced ATF3 translocated into the nucleus where TAp73? is expressed, but not in ATF3 (?C) or TAp73? siRNA–transfected cells. As confirmed by the GST pull-down assay, ATF3 bound to the DNA-binding domain of p73, resulting in the activation of p21 or Bax transcription, a downstream target of p73. Overexpression of ATF3 prolonged the half-life of TAp73? by inhibiting its ubiquitination and thereby enhancing its transactivation and proapoptotic activities. Additionally, ATF3 induced by paclitaxel potentiated the stability of TAp73?, not its transcriptional level. Chromatin immunoprecipitation analyses show that TAp73? and ATF3 are recruited directly to the p21 and Bax promoter. Collectively, these results reveal that overexpression of ATF3 potentiates paclitaxel-induced apoptosis of HeLa cells, at least in part, by enhancing TAp73?'s stability and its transcriptional activity. The investigation shows that ATF3 may function as a tumor-inhibiting factor through direct regulatory effects on TAp73?, suggesting a functional link between ATF3 and TAp73?. PMID:18644986

The 9-hydroxypheophorbide-? (9-HPbD) is a chlorophyll derivative and was found to be very effective for photodynamic therapy of tumor cells. The current study investigates uptake, retention, and intracellular localization of 9-HPbD by HeLa, human cervicalcancercells via fluorescence spectrophotometry and confocal laser scanning microscopy, and its photodynamic effect against human cervical carcinoma cell. HeLa cells exposed to 9-HPbD exhibited a linear uptake of photosensitizer during the first 12 h, and after removal of 9-HPbD, cell fluorescence was observed to decrease gradually over the next 12 h. Cells treated with 9-HPbD and stained with a panel of organelle-specific fluorescence probes (MitoTracker, LysoTracker, and ER-Tracker) revealed an intracellular fluorescence distribution restricted to cytoplasmic compartments with no detectable fluorescence in the nucleus. The 9-HPbD showed cytotoxicity effect against HeLa cells in 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Endoplasmic reticulum (ER) disruption and cellular calcium dynamics also showed a photoactivation followed by cell death. The apoptotic effect of 9-HPbD was confirmed by caspase 3 activity study and immunofluorescence study of caspase 12. Morphological observation through the transmission electron microscopy and scanning electron microscopy also confirmed that 9-HPbD can induce apoptosis in HeLa cells. Therefore, it can be concluded that maximum uptake and clearance time of 9-HPbD was 12 h with endoplasmic reticulum as the major organelle site in cellular uptake, and 9-HPbD can induce apoptosis in HeLa cells through ER stress-related pathways via activation of caspase 12. PMID:23649612

In recent years, the study of microRNAs associated with neoplastic processes has increased. Patterns of microRNA expression in different cell lines and different kinds of tumors have been identified; however, little is known about the alterations in regulatory pathways and genes involved in aberrant set of microRNAs. The identification of these altered microRNAs in several cervicalcancercells and potentially deregulated pathways involved constitute the principal goals of the present study. In the present work, the expression profiles of cellular microRNAs in CervicalCancer tissues and cell lines were explored using microRNA microarray, Affymetrix. The most over-expressed was miR-196a, which was evaluated by real time PCR, and HOXC8 protein as potential target by immunohistochemistry assay. One hundred and twenty three human microRNAs differentially expressed in the cell tumor, 64 (52%) over-expressed and 59 (48%) under-expressed were observed. Among the microRNAs over-expressed, we focused on miR-196a; at present this microRNA is poorly studied in CC. The expression of this microRNA was evaluated by qRT-PCR, and HOXC8 by immunohistochemistry assay. There is not a specific microRNA expression profile in the CC cells, neither a microRNA related to HPV presence. Furthermore, the miR-196a was over-expressed, while an absence of HOXC8 expression was observed. We suggest that miR-196a could be played as oncomiR in CC. PMID:24817935

The diversity and extent of the local tumor-specific T-cell response in a given individual is largely unknown. We have performed an in-depth study of the local T-cell repertoire in a selected group of patients with cervicalcancer, by systematic analyses of the proportion, breadth, and polarization of human papillomavirus (HPV) E6/E7-specific T cells within the total population of tumor-infiltrating lymphocytes (TIL) and tumor-draining lymph node cells (TDLNC). Isolated T cells were stimulated with sets of overlapping E6 and E7 peptides and analyzed by multiparameter flow cytometry with respect to activation, cytokine production, and T-cell receptor Vbeta usage. HPV-specific CD4+ and CD8+ T-cell responses were detected in TIL and TDLNC and their relative contribution varied between <1% and 66% of all T cells. In general, these HPV-specific responses were surprisingly broad, aimed at multiple E6 and E7 epitopes and involved multiple dominant and subdominant T-cell receptor Vbetas per single peptide-epitope. In most patients, only few IFNgamma-producing T cells were found and the amount of IFNgamma produced was low, suggesting that these are poised T cells, rendered functionally inactive within the tumor environment. Importantly, stimulation of the TIL and TDLNC with cognate antigen in the presence of commonly used Toll-like receptor ligands significantly enhanced the effector T-cell function. In conclusion, our study suggests that within a given patient with HPV-specific immunity many different tumor-specific CD4+ and CD8+ T cells are locally present and poised for action. This vast existing local T-cell population is awaiting proper stimulation and can be exploited for the immunotherapy of cancer. PMID:20233872

We previously found that snake venom toxin inhibits nuclear factor kappa B (NF-?B) activity in several cancercells. NF-?B is implicated in cancercell growth and chemoresistance. In our present study, we investigated whether snake venom toxin (SVT) inhibits NF-?B, thereby preventing human cervicalcancercell growth (Ca Ski and C33A). SVT (0-12 ?g/ml) inhibited the growth of cervicalcancercells by the induction of apoptotic cell death. These inhibitory effects were associated with the inhibition of NF-?B activity. However, SVT dose dependently increased the expression of death receptors (DRs): DR3, DR5 and DR downstream pro-apoptotic proteins. Exploration of NF-?B inhibitor (Phenylarsine oxide, 0.1 ?M) synergistically further increased SVT-induced DR3 and DR5 expressions accompanied with further inhibition of cancercells growth. Moreover, deletion of DR3 and DR5 by small interfering RNA significantly abolished SVT-induced cell growth inhibitory effects, as well as NF-?B inactivation. Using TNF-related apoptosis-inducing ligand resistance cancercells (A549 and MCF-7), we also found that SVT enhanced the susceptibility of chemoresistance of these cancercells through down-regulation of NF-?B, but up-regulation of DR3 and DR5. In vivo study also showed that SVT (0.5 and 1 mg/kg) inhibited tumor growth accompanied with inactivation of NF-?B. Thus, our present study indicates that SVT could be applicable as an anticancer agent for cervicalcancer, or as an adjuvant agent for chemoresistant cancercells. PMID:25417048

If left untreated, some cervical high-grade squamous intraepithelial lesions will progress to invasive squamous cell carcinoma (SCC), but the molecular events conferring invasive potential remain poorly defined. In prior work, we identified 48 genes that were down-regulated in SCCs compared with high-grade squamous intraepithelial lesions and normal squamous epithelia. In this study, a functional screening strategy was used to identify which of these genes regulate cervicalcancercell invasion. Two independent squamous epithelial cell lines were transduced with a library of short hairpin RNAs targeting the differentially expressed genes and tested for invasion of the chick chorioallantoic membrane. PCR was used to recover specific short hairpin RNAs from cells that invaded the chorioallantoic membrane. Constructs targeting estrogen receptor 1 (ESR1) were highly enriched in the invasive cells. The short hairpin RNA-mediated inhibition of ESR1 in SCC- and precancer-derived cell lines increased invasiveness in both in vivo and in vitro assays. Conversely, restoration of ESR1 expression in ESR1-negative cervicalcancercells reduced cell invasiveness. Loss of ESR1 expression was found to accompany cervicalcancer progression in an analysis of primary normal cervix, low grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and SCC specimens. Molecular mechanisms underlying down-regulation of ESR1 in invasive cervical carcinomas appear to be complex and likely heterogeneous. Our findings indicate that loss of ESR1 has a major role in mediating cervicalcancer invasion and progression. PMID:20581058

If left untreated, some cervical high-grade squamous intraepithelial lesions will progress to invasive squamous cell carcinoma (SCC), but the molecular events conferring invasive potential remain poorly defined. In prior work, we identified 48 genes that were down-regulated in SCCs compared with high-grade squamous intraepithelial lesions and normal squamous epithelia. In this study, a functional screening strategy was used to identify which of these genes regulate cervicalcancercell invasion. Two independent squamous epithelial cell lines were transduced with a library of short hairpin RNAs targeting the differentially expressed genes and tested for invasion of the chick chorioallantoic membrane. PCR was used to recover specific short hairpin RNAs from cells that invaded the chorioallantoic membrane. Constructs targeting estrogen receptor 1 (ESR1) were highly enriched in the invasive cells. The short hairpin RNA-mediated inhibition of ESR1 in SCC- and precancer-derived cell lines increased invasiveness in both in vivo and in vitro assays. Conversely, restoration of ESR1 expression in ESR1-negative cervicalcancercells reduced cell invasiveness. Loss of ESR1 expression was found to accompany cervicalcancer progression in an analysis of primary normal cervix, low grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and SCC specimens. Molecular mechanisms underlying down-regulation of ESR1 in invasive cervical carcinomas appear to be complex and likely heterogeneous. Our findings indicate that loss of ESR1 has a major role in mediating cervicalcancer invasion and progression. PMID:20581058

The novel biomarker LRIG3 is a member of the LRIG family (LRIG1-3). While LRIG1 has been associated with favorable prognosis and LRIG2 with poor prognosis in invasive cervicalcancer, little is known about the role of LRIG3. The aim of this study was to investigate the expression of LRIG3 in invasive cancer and cervical intraepithelial neoplasia (CIN) for possible correlation with other tumor markers, to hormones and smoking, as a diagnostic adjunct in CIN, and prognostic value in invasive cancer. Cervical biopsies from 129 patients with invasive squamous cell carcinoma and 170 biopsies showing low grade and high grade CIN, or normal epithelium were stained for LRIG3 and 17 additional tumor markers. Among other variables the following were included: smoking habits, hormonal contraceptive use, serum progesterone, serum estradiol, high-risk HPV-infection, menopausal status and ten-year survival. In CIN, high expression of the tumor suppressors retinoblastoma protein, p53, and p16, and E-cadherin (cell-cell interaction), or low expression of CK10, correlated to LRIG3 expression. In addition, progestogenic contraceptive use correlated to high expression of LRIG3. In invasive cancer there was a correlation between expression of the major tumor promoter c-myc and high LRIG3 expression. High LRIG3 expression correlated significantly to presence of high-risk HPV infection in patients with normal epithelium and CIN. There was no correlation between LRIG3 expression and 10-year survival in patients with invasive cellcervicalcancer. LRIG3 expression is associated with a number of molecular events in CIN. Expression also correlates to hormonal contraceptive use. The results on expression of other tumor markers suggest that LRIG3 is influenced by or influences a pattern of tumor markers in cancer and precancerous cells. Further studies are needed to elucidate if LRIG3 expression might be clinically useful. PMID:24998916

Background Decay-accelerating factor (DAF) and membrane cofactor protein (MCP) are the key molecules involved in cell protection against autologus complement, which restricts the action of complement at critical stages of the cascade reaction. The cooperative effect of DAF and MCP on the survival of human cervicalcancercell (ME180) has not been demonstrated. Methods In this study we applied, for the first time, short hairpin RNA (shRNA) to knock down the expression of the DAF and MCP with the aim of exploiting complement more effectively for tumor cell damage. Meanwhile, we investigated the cooperative effects of DAF and MCP on the viability and migration, moreover the proliferation of ME180 cell. Results The results showed that shRNA inhibition of DAF and MCP expression enhanced complement-dependent cytolysis (CDC) up to 39% for MCP and up to 36% for DAF, and the combined inhibition of both regulators yielded further additive effects in ME180 cells. Thus, the activities of DAF and MCP, when present together, are greater than the sum of the two protein individually. Conclusion These data indicated that combined DAF and MCP shRNA described in this study may offer an additional alternative to improve the efficacy of antibody-and complement-based cancer immunotherapy. PMID:19878546

Background Functional defects in mitochondria are involved in the induction of cell death in cancercells. The process of programmed cell death may occur through the mechanisms of apoptosis. Several potential lead molecules such as Camptothecin (CPT) and its analogues have been isolated from plants with anticancer effect. The aim of the present study was to understand the necrotic effect versus apoptotic nature of CPT in HeLa cancercells. Methods The anti-proliferative activity of CPT was estimated through 3-(4, 5- Dimethyl Thiazol-2-yl)-2, 5-diphenyl Tetrazolium bromide (MTT) assay and DNA fragmentation analysis using gel electrophoresis. Lactate Dehydrogenase (LDH) activity and cell morphology were assessed under control and CPT exposed conditions to evaluate the necrotic effect of CPT. Results The results showed that CPT inhibited the proliferation of HeLa cells in a dose-dependent manner with an Inhibitory Concentration 50% (IC50) of 0.08±0.012 µg/ml. However the significant (p<0.05) increase happens in LDH activity at concentrations 1×10-1µg/ml and above. Morphological changes showed that CPT in low concentrations induced an apoptotic mechanism of cell death, such as cell shrinkage and characteristic rounding of dying cells, while at high concentrations showed necrosis changes. The characteristic DNA ladder formation of CPT-treated cells in agarose gel electrophoresis confirmed the results obtained by light microscopy and LDH assay. Conclusion Camptothecin as an anticancer drug may have anti-proliferative effect on HeLa cancercells in low concentrations, through its nature of induction of apoptosis. The border line between necrotic effect and apoptotic nature of CPT in HeLa cancercells has been found to be at concentration of 1×10-1 µg/ml.

The objective of this study was to observe the apoptosis-inducing effect and mechanism of baicalin on human cervicalcancer HeLa cells. The inhibitory effect of baicalin on the growth of HeLa cells was measured by MTT assay, and cell proliferation and migration was analyzed by cell scratch assay. Morphological changes of apoptotic cells were viewed by the light microscope and electron microscope, and cell growth arrest was confirmed by flow cytometry. Moreover, Western blot was used for investigating the expression of apoptosis related proteins; spectrophotometry was used to examine Caspase-3 activation. Our results showed that baicalin could inhibit the proliferation of HeLa Cells via induction of apoptosis in a time and dose-dependent manner (P<0.01). Apoptotic signaling induced by baicalin was characterized by up-regulating Bax, Fas, FasL and Caspase-8 protein expression, and down-regulating of Bcl-2 protein expression. These results indicated that baicalin-induced apoptosis involved activation Caspase-3 in HeLa cells through the intracellular mitochondrial pathway and the surface death receptor pathway.

The objective of this study was to observe the apoptosis-inducing effect and mechanism of baicalin on human cervicalcancer HeLa cells. The inhibitory effect of baicalin on the growth of HeLa cells was measured by MTT assay, and cell proliferation and migration was analyzed by cell scratch assay. Morphological changes of apoptotic cells were viewed by the light microscope and electron microscope, and cell growth arrest was confirmed by flow cytometry. Moreover, Western blot was used for investigating the expression of apoptosis related proteins; spectrophotometry was used to examine Caspase-3 activation. Our results showed that baicalin could inhibit the proliferation of HeLa Cells via induction of apoptosis in a time and dose-dependent manner (P<0.01). Apoptotic signaling induced by baicalin was characterized by up-regulating Bax, Fas, FasL and Caspase-8 protein expression, and down-regulating of Bcl-2 protein expression. These results indicated that baicalin-induced apoptosis involved activation Caspase-3 in HeLa cells through the intracellular mitochondrial pathway and the surface death receptor pathway. PMID:25561931

Metastasis is the most common cause of cancer-related death in patients, and epithelial-to-mesenchymal transition (EMT) is essential for cancer metastasis, which is a multistep complicated process that includes local invasion, intravasation, extravasation, and proliferation at distant sites. When cancercells metastasize, angiogenesis is also required for metastatic dissemination, given that an increase in vascular density will allow easier access of tumor cells to circulation, and represents a rational target for therapeutic intervention. Berberine has several anti-inflammation and anticancer biologic effects. In this study, we provided molecular evidence that is associated with the antimetastatic effect of berberine by showing a nearly complete inhibition on invasion (P < 0.001) of highly metastatic SiHa cells via reduced transcriptional activities of matrix metalloproteinase-2 and urokinase-type plasminogen activator. Berberine reversed transforming growth factor-?1-induced EMT and caused upregulation of epithelial markers such as E-cadherin and inhibited mesenchymal markers such as N-cadherin and snail-1. Selective snail-1 inhibition by snail-1-specific small interfering RNA also showed increased E-cadherin expression in SiHa cells. Berberine also reduced tumor-induced angiogenesis in vitro and in vivo. Importantly, an in vivo BALB/c nude mice xenograft model and tail vein injection model showed that berberine treatment reduced tumor growth and lung metastasis by oral gavage, respectively. Taken together, these findings suggested that berberine could reduce metastasis and angiogenesis of cervicalcancercells, thereby constituting an adjuvant treatment of metastasis control. PMID:25217495

Hesperetin, a flavonoid from citrus fruits, has several bioactivities such as anti-inflammatory, antihypertensive, antiatherogenic effects. However, studies elucidating the role and the mechanism(s) of action of hesperetin in cervicalcancer are sparse. In this study, we investigated the mechanism of the antiproliferative and apoptotic actions exerted by hesperetin on human cervicalcancer SiHa cells. The viability of SiHa cells was evaluated using the MTT assay, apoptosis by acridine orange/ethidium bromide, propidium iodide, TUNEL assay, and Annexin V-Cy3, cell cycle distribution and mitochondrial transmembrane potential using flow cytometry, and apoptotic marker genes using quantitative real-time PCR. The treatment of SiHa cells with hesperetin (IC50, 650 ?m) showed a marked concentration- and time-dependent inhibition of proliferation and induced the G2/M phase in a dose-dependent manner after 24 h. There was an attenuation of mitochondrial membrane potential with increased expression of caspase-3, caspase-8, caspase-9, p53, Bax, and Fas death receptor and its adaptor protein Fas-associated death domain-containing protein (FADD), indicating the participation of both death receptor- and mitochondria-related mechanisms. Furthermore, hesperetin-induced apoptosis was confirmed by TUNEL and Annexin V-Cy3. This study shows that hesperetin exhibits a potential anticancer activity against human cervicalcancercell lines in vitro through the reduction in cell viability and the induction of apoptosis. Altogether, these data sustain our contention that hesperetin has anticancer properties and merits further investigation as a potential therapeutic agent. PMID:22913657

Noble metal nanoparticles have received considerable attention in biotechnology for their role in bio sensing due to surface plasmon resonance, medical diagnostics due to better imaging contrast and therapy. The radiosensitization effect of gold nanoparticles (AuNP) has been gaining popularity in radiation therapy of cancercells. The better depth dose profile of energetic ion beam proves its superiority over gamma radiation for fighting against cancer. In the present work, the glucose capped gold nanoparticles (Glu-AuNP) were synthesised and internalized in the HeLa cells. Transmission electron microscopic analysis of ultrathin sections of Glu-AuNP treated HeLa cells confirmed the internalization of Glu-AuNPs. Control HeLa cells and Glu-AuNp treated HeLa cells were irradiated at different doses of 62 MeV 12C ion beam (LET - 290keV/{mu}m) at BIO beam line of using 15UD Pelletron accelerator at Inter University Accelerator Centre, New Delhi, India. The survival fraction was assessed by colony forming assay which revealed that the dose of carbon ion for 90% cell killing in Glu-AuNP treated HeLa cells and control HeLa cells are 2.3 and 3.2 Gy respectively. This observation shows {approx} 28% reduction of {sup 12}C{sup 6+} ion dose for Glu-AuNP treated HeLa cells as compared to control HeLa cells.

Successful gene therapy requires safe and efficient gene vectors and gene delivery methods. This study is to investigate the effects of double suicide genes on the proliferation and apoptosis of HeLa cells by using the ultrasound-targeted microbubble destruction (UTMD). A lentiviral vector with the KDR promoter was constructed, packaged, and delivered into HeLa cells by UTMD. The results showed that the encapsulation efficiency was 90.6 ± 3.1% and the drug-loading efficiency was 29.2 ± 0.9% assessed by reversed-phase high performance liquid chromatography (RP-HPLC). Cell proliferation was determined by MTT assay and apoptosis was detected by flow cytometry. The proliferation rates of HeLa cells were significantly inhibited when treated with dual-gene lentiviral vectors or lentiviral vector-loaded microbubbles plus UTMD (P < 0.05). Moreover, the inhibiting effects were enhanced along with the increased ultrasonic intensities and declined at 24 h post-irradiation. Additionally, in comparison with the control group, the apoptotic rates of HeLa cells were significantly elevated in the lentiviral vector group and the lentiviral vector microbubble groups (P < 0.05). The apoptotic rates were also elevated as the ultrasonic irradiation intensities were increased (P < 0.05). The results suggest that dual-gene lentiviral vector-loaded microbubbles inhibit proliferation and enhance apoptosis of cervicalcancercells.

Background and purpose : The anticancer drug paclitaxel, a natural product from Taxus brevifolia, is a microtubule-stabilising agent, which has been shown to block different cells in the G2\\/M phase of the cell cycle and\\u000a so modulate their radioresponsiveness. We investigated the radiosensitizing potential of paclitaxel in human head and neck\\u000a cancercells (ZMK-1), in cervical squamous cell carcinoma cells (CaSki)

Cancer is a genetic and epigenetic disease. Multiple genetic and epigenetic changes have been studied in cervicalcancer; however, such changes are selected for during tumorigenesis and tumor aggression is not yet clear. Cervicalcancer is a multistep process with accumulation of genetic and epigenetic alterations in regulatory genes, leading to activation of oncogenes and inactivation or loss of tumor suppressor genes. In cervicalcancer, epigenetic alterations can affect the expression of papillomaviral as well as host genes in relation to stages representing the multistep process of carcinogenesis. PMID:25421689

Frutalin is the ?-D-galactose-binding lectin isolated from breadfruit seeds. Frutalin was obtained from two different sources: native frutalin was purified from its natural origin, and recombinant frutalin was produced and purified from Pichia pastoris. This work aimed to study and compare the effect of native and recombinant frutalin on HeLa cervicalcancercells proliferation and apoptosis. Furthermore, the interaction between frutalin and the HeLa cells was investigated by confocal microscopy. Despite having different carbohydrate-binding affinities, native and recombinant frutalin showed an identical magnitude of cytotoxicity on HeLa cells growth (IC50~100??g/mL) and equally induced cell apoptosis. The interaction studies showed that both lectins were rapidly internalised and targeted to HeLa cell's nucleus. Altogether, these results indicate that frutalin action is not dependent on its sugar-binding properties. This study provides important information about the bioactivity of frutalin and contributes to the understanding of the plant lectins cytotoxic activity. PMID:22131813

In recent years, long noncoding RNAs (lncRNAs) have been demonstrated to play key roles in tumorgenesis. However, the contributions of lncRNAs to cervicalcancer (CC) remain largely unknown. In this study, differentially expressed lncRNAs and mRNAs in cervicalcancer and paired peritumoral tissues were detected by transcriptome microarray analysis. We found 708 probe sets of lncRNAs increased and 836 probe sets decreased in CC tissues, while 1288 mRNA differential probe sets increased and 901 mRNA probe sets decreased. The results were validated by quantitative real-time polymerase chain reaction (qPCR). Then, we found a specific differentially expressed lncRNA can physically bind to enhancer of zeste homolog2 (EZH2) by using RNA immunoprecipitation. We termed it as EZH2-binding lncRNA in cervicalcancer [lncRNA-EBIC]. Wound healing assays and Matrigel invasion assays were used to determine the function of this lncRNA by silencing it. We observed that the migration and invasion of cervicalcancercells in vitro were inhibited upon suppression of lncRNA-EBIC by siRNA. We also found that the association between lncRNA-EBIC and EZH2 was required for the repression of E-cadherin, which was a key molecular in the metastasis of cervicalcancer. Conclusion These results demonstrated that lncRNA-EBIC was an oncogenic lncRNA, which could promote tumor cell invasion in CC by binding to EZH2 and inhibiting E-cadherin expression. PMID:25007342

Many anticancer drugs have been established clinically, but their efficacy can be compromised by nonspecific toxicity and an inability to reach the desired cancerous intracellular spaces. In order to address these issues, researchers have explored the use of folic acid as a targeted moiety to increase specificity of chemotherapeutic drugs. To expand upon such research, we have conjugated folic acid to functionalized poly(ethylene glycol) and subsequently decorated the surface of L-tyrosine polyphosphate (LTP) nanoparticles. These nanoparticles possess the appropriate size (100–500 nm) for internalization as shown by scanning electron microscopy and dynamic light scattering. Under simulated physiological flow, LTP nanoparticles decorated with folic acid (targeted nanoparticles) show a 10-fold greater attachment to HeLa, a cervicalcancercell line, compared to control nanoparticles and to human dermal fibroblasts. The attachment of these targeted nanoparticles progresses at a linear rate, and the strength of this nanoparticle attachment is shown to withstand shear stresses of 3.0 dynes/cm2. These interactions of the targeted nanoparticles to HeLa are likely a result of a receptor-ligand binding, as a competition study with free folic acid inhibits the nanoparticle attachment. Finally, the targeted nanoparticles encapsulated with a silver based drug show increased efficacy in comparison to non-decorated (plain) nanoparticles and drug alone against HeLa cells. Thus, targeted nanoparticles are a promising delivery platform for developing anticancer therapies that over-express the folate receptors (FRs). PMID:22957928

Cervicalcancer is the second most common cancer in women worldwide. It represents one of the most challenging public health problems in developing countries. HIV-infected women have a higher risk of cervicalcancer which is an AIDS defining cancer. Cervicalcancer treatment in HIV-infected and non-infected women is the same. HIV naive women must be prescribed combination antiretroviral therapy at the moment of HIV cancer diagnosis. A close collaboration between oncologist and infectiologist is mandatory to optimize HIV treatment. Among HIV-infected women, PAP-smear screening for early detection and treatment of precancerous cervical lesions is recommended. HPV vaccination is also recommended with the same efficacy and safety profile as the general population. PMID:25418597

NCI funded a clinical trial that will have an impact on the treatment of late-stage cervicalcancer, and also supported a screening trial in India using a network of community outreach workers offering low tech-screening by direct visualization of the cervix coated with dilute acetic acid (vinegar), a process known as VIA. Image depicts cervicalcancer microvessel density which increases lethality of the cancer.

Background Emodin is a natural anthraquinone derivative isolated from the Rheum palmatum L. Aim: The aim of the present study was to investigate the effect of emodin on the apoptosis of the human cervicalcancer line HeLa and to identify the mechanisms involved. Methods Relative cell viability was assessed by MTT assay after treatment with emodin. Cell apoptosis was detected with TUNEL, Hoechst 33342 staining and quantified with flow cytometry using annexin FITC-PI staining. Results The percentage of apoptotic cells was 0.8, 8.2, 22.1, and 43.7%, respectively. The mRNA levels of Caspase-9, -8 and ?3 detected by Real-time PCR after treatment with emodin were significantly increased. Emodin increased the protein levels of Cytochome c, Apaf-1, Fas, FasL, and FADD but decreased the protein levels of Pro-caspase-9, Pro-caspase-8 and Pro-caspase-3. Conclusion We conclude that the emodin inhibited HeLa proliferation by inducing apoptosis through the intrinsic mitochondrial and extrinsic death receptor pathways. PMID:23866157

High-risk human papillomavirus (HR-HPV) has been recognized as a major causative agent for cervicalcancer. Upon HPV infection, early genes E6 and E7 play important roles in maintaining malignant phenotype of cervicalcancercells. By using clustered regularly interspaced short palindromic repeats- (CRISPR-) associated protein system (CRISPR/Cas system), a widely used genome editing tool in many organisms, to target HPV16-E7 DNA in HPV positive cell lines, we showed for the first time that the HPV16-E7 single-guide RNA (sgRNA) guided CRISPR/Cas system could disrupt HPV16-E7 DNA at specific sites, inducing apoptosis and growth inhibition in HPV positive SiHa and Caski cells, but not in HPV negative C33A and HEK293 cells. Moreover, disruption of E7 DNA directly leads to downregulation of E7 protein and upregulation of tumor suppressor protein pRb. Therefore, our results suggest that HPV16-E7 gRNA guided CRISPR/Cas system might be used as a therapeutic strategy for the treatment of cervicalcancer. PMID:25136604

Fertility can be preserved after conservative cervical surgery. We report on a 29-year-old woman who was obese, para 0, and diagnosed with cervical insufficiency at the first trimester of current pregnancy due to a previous trachelectomy. She underwent laparoscopic transabdominal cervical cerclage (LTCC) for cervicalcancer. The surgery was successful and she was discharged two days later. The patient underwent a caesarean section at 38 weeks of gestation. Laparoscopic surgery is a minimally invasive approach associated with less pain and faster recovery, feasible even in obese women. PMID:24696772

Cervicalcancer is an issue of foremost importance globally, specifically affecting the developing nations. Significant advances have taken place with regard to diagnosis of cervicalcancer, especially with screening. Appropriate screening measures can thus reduce the incidence of cervicalcancer. The most desirable screening technique should be less invasive, easy to perform, cost-effective and cover a wide range of diagnostic icons. Manual liquid based cytology (MLBC) can be considered as one of the suitable technique for screening with the above-mentioned benefits. The aim of the current study was to compare two cervical screening techniques on the basis of different morphological parameters and staining parameters by using modified acetic acid Pap staining to see the possibility of reducing time economy involved in conventional Pap staining (CPS). The study was conducted on a total 88 cases and all were analyzed with both MLBC and CPS. Forty eight cases that were regarded as satisfactory on the basis of Bethesda system by both methods were further recruited for investigation. Their morphological parameters and staining quality were compared and scored according to a scoring system defined in the study. Quality indices was calculated for both staining procedures and smear techniques. PMID:24568528

The aim of this study was to describe the state of the art in cervicalcancer screening in Greece by presenting the two regionally organised screening programmes that currently operate in the country. Both programmes were initiated in 1991 and are partly funded by the European Union. The Ormylia screening programme covers the population of Halkidiki (Northern Greece), a predominantly rural area. The second programme covers the regions of Messinia and Ilia (Southern Greece). Both programmes are targeted at women aged 25-64 years of age and a Papanicolaou (Pap) smear test is recommended every 2-3 years. Electoral and municipal registries are used to identify the target population and personal invitations are sent to the eligible women in the screening programme. The Ormylia programme is based at the Centre 'Our Lady Who Loves Mankind', whereas mobile units are used by the Messinia and Ilia programme. Slide reading for the Ormylia programme is performed in the cytology laboratory of Alexandra Hospital in Athens and epidemiological support is provided by the Department of Hygiene and Epidemiology (Medical School, University of Athens). A specifically designed database is used for data recording. Over 80% of the target population in the region have already been screened. Communication of results is by means of a personal letter upon a negative result and in person upon a suspicious result. Quality assurance in both programmes is based on the European protocol. These two programmes are the sole organised cervicalcancer screening activities in Greece in the absence of a national programme. They employ well-trained personnel, they use modern equipment and have strict quality assurance procedures. PMID:11072209

Dr. Monk is nationally recognized for his expertise in cervicalcancer and chairs the Gynecologic Oncology CervicalCancer Committee for the National Cancer Institute funded Gynecologic Oncology Group for the study published in NEJM.

RNA interference is a natural mechanism to silence post-transcriptional gene expression in eukaryotic cells in which microRNAs act to cleave or halt the translation of target mRNAs at specific target sequences. Mature microRNAs, 19-25 nucleotides in length, mediate their effect at the mRNA level by inhibiting translation, or inducing cleavage of the mRNA target. This process is directed by the degree of complementary nucleotides between the microRNAs and the target mRNA; perfect complementary base pairing induces cleavage of mRNA, whereas several mismatches lead to translational arrest. Biological effects of microRNAs can be manipulated through the use of small interference RNAs (siRNAs) generated by chemical synthesis, or by cloning in molecular vectors. The cloning of a DNA insert in a molecular vector that will be transcribed into the corresponding siRNAs is an approach that has been developed using siRNA expression plasmids. These vectors contain DNA inserts designed with software to generate highly efficient siRNAs which will assemble into RNA-induced silencing complexes (RISC), and silence the target mRNA. In addition, the DNA inserts may be contained in cloning cassettes, and introduced in other molecular vectors. In this chapter we describe an attractive technology platform to silence cellular gene expression using specific siRNA expression plasmids, and evaluate its biological effect on target gene expression in human cervicalcancercells. PMID:25348304

Purpose: To assess the clinical value of FDG PET/CT and evaluate the complementary roles of serum squamous cell carcinoma antigen (SCCAg) and FDG PET/CT in the diagnosis of suspected recurrent of cervical squamous cellcancer. Methods: Serum SCCAg levels were retrospectively reviewed in patients previously treated for cervical squamous cell carcinoma, who had suspected recurrence of cervicalcancer and who had undergone FDG PET/CT scans. The clinical impact of elevated SCCAg (>1.5 ng/ml) and negative SCCAg (?1.5 ng/ml) levels were analyzed based on the results of PET/CT and final diagnosis. Results: The overall patient-based sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of PET/CT for the detection of tumor recurrence or malignancy were 100% (86/86), 80.8% (21/26), 95.5% (107/112), 94.5% (86/91) and 100% (21/21), respectively. Of the 112 patients included in this study, recurrence or malignancy was detected by PET/CT in 62 of the 64 patients with elevated SCCAg, compared to 24 of the 48 patients with negative SCCAg levels. The overall patient-based PPV, NPV, sensitivity and accuracy of SCCAg for the detection of tumor recurrence or malignancy were 96.9% (62/64), 50% (24/48), 72.1% (62/86) and 76.8% (86/112), respectively. The five false-positive PET/CT results were all associated with patients with negative SCCAg levels. The PPV of positive PET/CT-associated elevated SCCAg for the detection of tumor recurrence or malignancy was 100% (62/62). The NPV of negative SCCAg-associated negative PET/CT was 100% (19/19). Conclusions: Serum SCCAg evaluation and FDG PET/CT imaging can be complementary techniques in cases of suspected recurrent cervical squamous cancer. Positive PET/CT with elevated SCCAg can predict recurrence. Although PET/CT cannot confidently be deferred due to a negative SCCAg test, the possibility of a false-positive PET/CT in those cases may have diagnostic importance. PMID:25663947

Cervicalcancer, mainly caused by Human Papillomavirus infection, is the leading cancer in Indian women and the second most common cancer in women worldwide. Though there are several methods of prevention of cervicalcancer, prevention by vaccination is emerging as the most effective option, with the availability of two vaccines. Several studies have been published examining the vaccine's efficacy, immunogenicity and safety. Questions and controversy remain regarding mandatory vaccination, need for booster doses and cost-effectiveness, particularly in the Indian context. PMID:22754202

Human papillomaviruses (HPVs) is the principal etiological agent of cervicalcancer (CC). However, exposure to the high-risk type HPV alone is insufficient for tumor formation, and additional factors are required for the HPV-infected cells to become tumorigenic. Dysregulated microRNAs (miRNAs) expression is frequently observed in cancer but their roles in the formation of CC have not been fully revealed. In this study, we compared the expression of miR-135a in laser capture microdissected cervical specimens and confirmed overexpression of the miRNA in malignant cervical squamous cell carcinoma compared with precancerous lesions. Transient force-expression of miR-135a induced growth in low-density culture, anchorage-independent growth, proliferation and invasion of a HPV-16 E6/E7-immortalized cervical epithelial cell line, NC104-E6/E7. The observed effects were due to the inhibitory action of miR-135a on its direct target seven in absentia homolog 1 (SIAH1) leading to upregulation of ?-catenin/T cell factor signaling. miR-135a force-expression enhanced the growth of HeLa- and NC104-E6/E7-derived tumor in vivo. The effect of miR-135a could be partially nullified by SIAH1 force-expression. More importantly, the expression of SIAH1 and ?-catenin correlated with that of miR-135a in precancerous and cancerous lesions of cervical biopsies. By comparing the tumorigenic activities of miR-135a in E6/E7 positive/negative cell lines and in NC104-E6/E7 with or without E6/E7 knockdown, we demonstrated that HPV E6/E7 proteins are prerequisite for miR-135a as an oncomiR. Taken together, miR-135a/SIAH1/?-catenin signaling is important in the transformation and progression of cervical carcinoma. PMID:24503442

Nuclear expression of ?-catenin has been suggested as an independent prognostic marker in a variety of cancers. The objective of this study was to investigate the clinicopathologic significance of nuclear ?-catenin expression in patients with cervical squamous cell carcinoma (CSCC). In this original research article, we detected nuclear ?-catenin expression in 29/171 CSCC tissues (17.0%). Patients without nuclear ?-catenin expression had a significantly better outcome than patients with nuclear ?-catenin expression (93.7% versus 82.7% P = 0.027). Furthermore, nuclear ?-catenin expression was predictive of prognosis in CSCC patients with early stage disease (FIGO stage I or tumor size ? 4 cm), with well/moderately differentiated tumors, or lymph node metastasis. Interestingly, nuclear ?-catenin expression correlated with poor outcome in patients who received postoperative chemotherapy or radiotherapy. Multivariate analysis suggested that nuclear ?-catenin expression is an independent prognostic indicator in CSCC. Our findings suggest that nuclear ?-catenin expression may be used as a prognostic biomarker in CSCC, especially for patients with early stage disease, well/moderately differentiated tumors, or lymph node metastasis. Moreover, nuclear ?-catenin expression has potential as a predictive marker of chemoresistance and radioresistance in CSCC. PMID:25120767

Although fully treatable in the early stages, once cervicalcancer has metastasized, patient outcome is poor. The main objective of this study was to examine the effect of dietary supplementation with a nutrient mixture (NM) containing lysine, ascorbic acid, proline, green tea extract and other micronutrients on HeLa cell xenografts in nude female mice. Tumor growth was measured and immunohistochemical staining was evaluated for the following cancer markers: Ki67 (proliferation); matrix metalloproteinase (MMP)-2 and -9 (invasion/metastasis); vascular endothelial growth factor (VEGF) (angiogenesis); terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and B-cell lymphoma 2 (Bcl-2) (apoptosis); cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) (inflammation); and glutathione S-transferase ? (GST?) (a general cancer marker). Following housing for a week, 5/6-week-old female athymic nude mice (n=12) were inoculated subcutaneously with 3×106 HeLa cells in 0.2 ml phosphate-buffered saline and 0.1 ml Matrigel™ and randomly divided into two groups; control group mice were fed regular mouse chow and NM group mice the regular diet supplemented with 0.5% NM (w/w). After four weeks, the mice were sacrificed and their tumors were excised and processed for histology. The NM strongly inhibited the growth of HeLa xenografts in nude mice. The mean tumor weight was reduced to 59% (P=0.001) in the mice fed the NM compared with the tumor weight in the controlled diet mice. Ki67, MMP-2 and -9, VEGF, TUNEL, Bcl-2, COX-2, iNOS and GST? all showed a lower intensity and frequency of staining in the NM group compared with that in the control group. In conclusion, NM supplementation strongly inhibited tumor growth and cancer markers in female nude mice injected with HeLa xenografts. PMID:25574189

Human papillomavirus (HPV), especially HPV 16, is associated with the development of both cervical and oral cancer. We show the case of a woman affected by HPV-related cervical disease and oropharyngeal squamous cell carcinoma (OPSCC). A 41-year-old woman arrived at our Colposcopy Center following an abnormal Pap smear result (ASC-H) and a diagnosis of moderate cervical dysplasia obtained by a cervical biopsy. She underwent a colposcopy that showed a cervical abnormal transformation zone grade 2. A laser conization was performed in November 2010. Histology reported a moderate/severe dysplasia. The cone resection margins were free. Follow-up colposcopy and cytology were negative. The HPV testing showed an infection by HPV 16. In October 2012, the patient presented to the Head-Neck ER after episodes of hemoptysis; a lesion was found in the left tonsillar lodge. A biopsy was performed with a result of squamous cell carcinoma with low-grade differentiation. The HPV testing detected a high-risk HPV and the immunohistochemical analysis was positive for p16. She was treated by chemotherapy and brachytherapy. She was followed at the head-neck center with monthly visits with oral visual inspection that showed complete absence of mucosal abnormalities. HPV-related OPSCC and cervical precancerous/cancerous lesions have significant similarities in terms of pathogenesis. They are both caused largely by HPV 16, as in the present case. In conclusion, because of this association found in literature and in our case, we think that women with HPV cervical lesions should have regular surveillance for oropharyngeal cancer, whereas women with OPSCC should be encouraged to have diligent cervical screening. PMID:24584479

Cervicalcancer is the second most frequent malignancy affecting women worldwide. The highest incidences occur in the developing world, where, in most countries, cervicalcancer is the leading cause of cancer mortality in women. Although surgery and chemoradiotherapy can cure 80-95% of women with early stage cancer and 60% of locoregionally advanced cancer, the recurrent and metastatic disease remains a major cause of cancer death. The current cytotoxic treatment options for advanced and metastatic cancer demonstrate modest results, with response rates of maximum 30% and overall survival of less than 10 months. Given this limited degree of success with conventional therapies, interest has increased in other therapeutic alternatives. In this way, targeted agents are emerging as potential candidates for improving survival in cervicalcancer patients. In this review we highlight the main current therapeutic strategies for cervicalcancer and summarize the most relevant patents from the latest five years. Special attention was given to patents with potential applications in the clinical practice. PMID:19522698

Leea indica is a medicinal plant traditionally used to treat cancer. Through bioassay-guided approach, we isolated mollic acid arabinoside (MAA), for the first time from Leea indica. Here, we present the apoptosis-inducing effect of MAA on Ca Ski cervicalcancercells. Based on DAPI staining, MAA-treated cells manifested nuclear shrinkage, condensation, and fragmentation. We further confirmed the fragmentation of DNA using TUNEL assay. During early apoptosis, MAA caused the perturbation of plasma membrane through externalization of PS, followed by the formation of apoptotic blebs. Prior to these events, MAA triggered rapid dissipation of the mitochondrial membrane potential. In the upstream, MAA increased the expression of Bax, decreased the expression of Bcl-2, and augmented the Bax/Bcl-2 ratio. These findings suggested that MAA induced mitochondrial-mediated apoptosis in Ca Ski cells and thus provide the scientific explanation for the traditional application of this herbal medicine in cancer treatment. PMID:22203877

segmentation of cells. In this paper, we propose a two- phase approach to cell segmentation in Pap smear test cancer can be prevented if it is detected and treated early. Pap smear test is a manual screening-assisted screening system for Pap smear tests will be very beneficial to prevent cervicalcancer if it increases

Abstract Background. The Faroe Islands have had nationally organised cervicalcancer screening since 1995. Women aged 25-60 years are invited every third year. Participation is free of charge. Although several European overviews on cervical screening are available, none have included the Faroe Islands. Our aim was to provide the first description of cervicalcancer screening, and to determine the screening history of women diagnosed with cervicalcancer in the Faroe Islands. Material and methods. Screening data from 1996 to 2012 were obtained from the Diagnostic Centre at the National Hospital of the Faroe Islands. They included information on cytology and HPV testing whereas information on histology was not registered consistently. Process indicators were calculated, including coverage rate, excess smears, proportion of abnormal cytological samples, and frequency of HPV testing. Data on cervicalcancer cases were obtained from the Faroese Ministry of Health Affairs. The analysis of the screening history was undertaken for cases diagnosed in 2000-2010. Results. A total of 52 457 samples were taken in 1996-2012. Coverage varied between 67% and 81% and was 71% in 2012. Excess smears decreased after 1999. At present, 7.0% of samples have abnormal cytology. Of all ASCUS samples, 76-95% were tested for HPV. A total of 58% of women diagnosed with cervicalcancer did not participate in screening prior to their diagnosis, and 32% had normal cytology in the previous four years. Conclusion. Despite the difficult geographical setting, the organised cervicalcancer screening programme in the Faroe Islands has achieved a relatively high coverage rate. Nevertheless, challenges, e.g. consistent histology registration and sending reminders, still exist. PMID:25495570

Cervicalcancer can be prevented with HPV vaccines. NCI-supported researchers helped establish HPV as a cause of cervicalcancer. They also helped create the first HPV vaccines, were involved in the vaccine trials, and contribute to ongoing studies.

We developed a discovery-validation mass-spectrometry-based pipeline to identify a set of proteins that are regulated in serum of patients with cervical intraepithelial neoplasia (CIN) and squamous cellcervicalcancer using iTRAQ, label-free shotgun, and targeted mass-spectrometric quantification. In the discovery stage we used a "pooling" strategy for the comparative analysis of immunodepleted serum and revealed 15 up- and 26 down-regulated proteins in patients with early- (CES) and late-stage (CLS) cervicalcancer. The analysis of nondepleted serum samples from patients with CIN, CES, an CLS and healthy controls showed significant changes in abundance of alpha-1-acid glycoprotein 1, alpha-1-antitrypsin, serotransferrin, haptoglobin, alpha-2-HS-glycoprotein, and vitamin D-binding protein. We validated our findings using a fast UHPLC/MRM method in an independent set of serum samples from patients with cervicalcancer or CIN and healthy controls as well as serum samples from patients with ovarian cancer (more than 400 samples in total). The panel of six proteins showed 67% sensitivity and 88% specificity for discrimination of patients with CIN from healthy controls, a stage of the disease where current protein-based biomarkers, for example, squamous cell carcinoma antigen (SCCA), fail to show any discrimination. Additionally, combining the six-protein panel with SCCA improves the discrimination of patients with CES and CLS from healthy controls. PMID:25232869

Cervicalcancer is one of the most common cancers among women in the world. 6-Shogaol is a natural compound isolated from the rhizome of ginger (Zingiber officinale). In this paper, we demonstrated that 6-shogaol induced apoptosis and G2/M phase arrest in human cervicalcancer HeLa cells. Endoplasmic reticulum stress and mitochondrial pathway were involved in 6-shogaol-mediated apoptosis. Proteomic analysis based on label-free strategy by liquid chromatography chip quadrupole time-of-flight mass spectrometry was subsequently proposed to identify, in a non-target-biased manner, the molecular changes in cellular proteins in response to 6-shogaol treatment. A total of 287 proteins were differentially expressed in response to 24 h treatment with 15 ?M 6-shogaol in HeLa cells. Significantly changed proteins were subjected to functional pathway analysis by multiple analyzing software. Ingenuity pathway analysis (IPA) suggested that 14-3-3 signaling is a predominant canonical pathway involved in networks which may be significantly associated with the process of apoptosis and G2/M cell cycle arrest induced by 6-shogaol. In conclusion, this work developed an unbiased protein analysis strategy by shotgun proteomics and bioinformatics analysis. Data observed provide a comprehensive analysis of the 6-shogaol-treated HeLa cell proteome and reveal protein alterations that are associated with its anticancer mechanism. PMID:23243437

Ganoderic acid T, a triterpenic acid produced by Ganoderma lucidum, has demonstrated therapeutic potential for tumor disease. In the current work, ganoderic acid T was modified to produce more effective small-molecule inhibitors of cancercell proliferation. Moreover, the anticancer effects of three new ganoderic acid T derivatives, i.e., (22S,24E)-3?,15?,22-triacetoxy-5?-lanosta-7,9(11),24-trien-26-oic acid ethyl ester (TLTO-Ee), (22S,24E)-3?,15?,22-triacetoxy-5?-lanosta-7,9(11),24-trien-26-oic acid propyl ester (TLTO-Pe), and (22S,24E)-3?,15?,22-triacetoxy-5?-lanosta-7,9(11),24-trien-26-oic acid amide (TLTO-A), and one known derivative, (22S,24E)-3?,15?,22-triacetoxy-5?-lanosta-7,9(11),24-trien-26-oic acid methyl ester (TLTO-Me), on the cervicalcell line HeLa were investigated and compared. MTT assay indicated that, among the tested compounds, TLTO-A displayed the highest inhibitory effect on the growth of HeLa cells, whereas it showed less cytotoxicity to the non-tumorous cell line MCF-10A than ganoderic acid T. Flow cytometry analysis revealed that all the compounds caused cell cycle arrest at the G1 phase and induced apoptosis. Furthermore, they decreased the mitochondrial membrane potential and enhanced the activities of pro-apoptotic factors caspase-3 and caspase-9 in a dose-dependent manner. Accordingly, the apoptosis induction was presumed to occur through the endogenous pathway. The following order ranks both cytotoxic and pro-apoptotic effects of the compounds against HeLa cells: TLTO-A>ganoderic acid T?TLTO-Me?TLTO-Ee?TLTO-Pe. This study suggests that the carboxyl group of ganoderic acid T is not the main active group and is suitable for its further structural modification. The current work presents valuable information on the design of ganoderic acid T derivatives to develop potential chemotherapy agents. PMID:22366428

Alteration of the apoptosis pathway, as well as the presence of human papilloma virus (HPV), has been linked to the proliferative capacity and drug resistant phenotype of SiHa cervicalcancer. We investigated the roles of E6 and E7 HPV oncoproteins in the expression of apoptosis regulating genes in cervicalcancercells that contain the characteristics of apoptosis resistance, and also

Summary We contrast the efforts to treat ovarian cancer and cervicalcancer through vaccination because of their different pathobiology. A plethora of approaches have been developed for therapeutic vaccination against cancer, many of which target defined tumor-associated antigens (TAAs). Persistent infection with oncogenic human papillomavirus (HPV) types is necessary cause of cervicalcancer. Furthermore, cervicalcancer patients frequently mount both humoral and T cell immune responses to the HPV E6 and E7 oncoproteins, whose expression is required for the transformed phenotype. Numerous vaccine studies target these viral TAAs, including recent trials that may enhance clearance of pre-malignant disease. By contrast little is known about the etiology of epithelial ovarian cancer. Although it is clear that p53 mutation or loss is a critical early event in the development of epithelial ovarian cancer, no precursor lesion has been described for the most common serous histotype, and even the location of its origin is debated. These issues have complicated the selection of appropriate ovarian TAAs and the design of vaccines. Here we focus on mesothelin as a promising ovarian TAA because it is overexpressed and immunogenic at high frequency in patients, is displayed on the cell surface and potentially contributes to ovarian cancer biology. PMID:18363994

The aim of this study was to determine whether the codon 31 genotype of p21 might be associated with an increased risk of cervicalcancer development in Korean women. We used tissue derived from patients with invasive cervicalcancer (ICC) (n=111, composed of two histologic groups: squamous cell carcinoma (n=67) and adenocarcinoma (n=44)), cervical intraepithelial neoplasia (CIN) III (n=101), and

Virtually all cervicalcancers are caused by HPV infections, with just two HPV types, 16 and 18, responsible for about 70 percent of all cases, according to the National Cancer Institute. Scientists have presumed for decades that the cervicalcancers that develop from HPV infection arise in a specific location in the cervix. Now, new research from Brigham and Women's Hospital (BWH) in close collaboration with Harvard Medical School and the Agency for Science Technology and Research in Singapore finds that a specific population of cells that are found only in the region of the cervix called the "squamo-columnar junction" can become cancerous when infected with HPV while other cells in the cervix apparently do not. This research is published online the week of June 11 in the Proceedings of the National Academy of Sciences (PNAS).

The anti–epidermal growth factor receptor (anti-EGFR) antibody cetuximab is clinically approved for the treatment of EGFR-expressing metastatic colorectal cancer and advanced head and neck cancer. Overexpression of EGFR has also been found in more than 70% of carcinomas of the cervix. The overall goal of this study was to determine whether 64Cu-1,4,7,10-tetraazacyclododecane-N,N?, N??N???-tetraacetic acid (DOTA)-cetuximab has potential as an agent for measuring EGFR concentration by PET imaging in cervicalcancer tumors. Methods Cetuximab was conjugated to the bifunctional chelator DOTA and labeled with 64Cu. EGFR messenger RNA (mRNA) expression was correlated with EGFR densities on the cell surface of 5 different cervicalcancercell lines and with receptor function, measured by internalization of 64Cu-DOTA-cetuximab. Imaging in tumor-bearing mice with small-animal PET was performed using the highest-expressing cervicalcancercell line. Results The affinity of 64Cu-DOTA-cetuximab binding for the EGFR was similar in 4 EGFR-positive lines, varying from 0.1 to 0.7 nM. The mRNA expression corresponded well with EGFR densities and levels of internalization, with responses decreasing in the order of CaSki > ME-180 > DoTc2 4510 > HeLa > C-33A. Biodistribution and small-animal PET studies with 64Cu-DOTA-cetuximab in CaSki tumor-bearing nude mice showed relatively high tumor uptake at 24 h after injection (13.2 ± 1.2 percentage of injected activity per gram), although there was also significant retention of activity in the blood and liver accumulation. Conclusion 64Cu-DOTA-cetuximab was successfully used to detect and quantify EGFR expression in cervicalcancer tumors, and small-animal PET/CT of EGFR-expressing CaSki tumors suggests potential for PET/CT of EGFR-positive tumors. PMID:18703609

High-risk human papillomavirus (HPV), especially HPV16, is considered a main causative agent of cervicalcancer. Upon HPV infection, the viral oncoprotein E6 disrupts the host tumor-suppressor protein p53, thus promoting malignant transformation of normal cervicalcells. Here, we used the newly developed programmable ribonucleic acid-guided clustered regularly interspaced short palindromic repeat (CRISPR)/Cas system to disrupt the HPV16 E6 gene. We showed that HPV16 E6 deoxyribonucleic acid was cleaved at specific sites, leading to apoptosis and growth inhibition of HPV16-positive SiHa and CaSki cells, but not HPV-negative C33A or human embryonic kidney 293 cells. We also observed downregulation of the E6 protein and restoration of the p53 protein. These data proved that the HPV16 E6 ribonucleic acid-guided CRISPR/Cas system might be an effective therapeutic agent in treating HPV infection-related cervical malignancy. PMID:25565864

High-risk human papillomavirus (HPV), especially HPV16, is considered a main causative agent of cervicalcancer. Upon HPV infection, the viral oncoprotein E6 disrupts the host tumor-suppressor protein p53, thus promoting malignant transformation of normal cervicalcells. Here, we used the newly developed programmable ribonucleic acid-guided clustered regularly interspaced short palindromic repeat (CRISPR)/Cas system to disrupt the HPV16 E6 gene. We showed that HPV16 E6 deoxyribonucleic acid was cleaved at specific sites, leading to apoptosis and growth inhibition of HPV16-positive SiHa and CaSki cells, but not HPV-negative C33A or human embryonic kidney 293 cells. We also observed downregulation of the E6 protein and restoration of the p53 protein. These data proved that the HPV16 E6 ribonucleic acid-guided CRISPR/Cas system might be an effective therapeutic agent in treating HPV infection-related cervical malignancy. PMID:25565864

The transcription factor grainyhead-like 2 (GRHL2) is evolutionarily conserved in many different species, and is involved in morphogenesis, epithelial differentiation, and the control of the epithelial-mesenchymal transition. It has also recently been implicated in carcinogenesis, but its role in this remains controversial. Expression of GRHL2 has not previously been reported in cervicalcancer, so the present study aimed to characterize GRHL2 expression in cervicalcancer-derived cell lines (CCCLs) and cervical tissues with different grades of lesions. Microarray analysis found that the expression of 58 genes was down-regulated in CCCLs compared to HaCaT cells (non-tumorigenic human epithelial cell line). The expression of eight of these genes was validated by quantitative real-time PCR (qPCR), and GRHL2 was found to be the most down-regulated. Western blot assays corroborated that GRHL2 protein levels were strongly down-regulated in CCCLs. Cervicalcells from women without cervical lesions were shown to express GRHL2, while immunohistochemistry found that positivity to GRHL2 decreased in cervicalcancer tissues. In conclusion, a loss or strong reduction in GRHL2 expression appears to be a characteristic of cervicalcancer, suggesting that GRHL2 down-regulation is a necessary step during cervical carcinogenesis. However, further studies are needed to delineate the role of GRHL2 in cervicalcancer and during malignant progression.

Standard treatment of cervicalcancer (CC) consists of surgery in the early stages and of chemoradiation in locally advanced disease. Metastatic CC has a poor prognosis and is usually treated with palliative platinum-based chemotherapy. Current chemotherapeutic regimens are associated with significant adverse effects and only limited activity, making identification of active and tolerable novel targeted agents a high priority. Angiogenesis is a complex process that plays a crucial role in the development of many types of cancer. The dominant role of angiogenesis in CC seems to be directly related to human papillomavirus-related inhibition of p53 and stabilization of hypoxia-inducible factor-1?. Both of these mechanisms are able to increase expression of vascular endothelial growth factor (VEGF). Activation of VEGF promotes endothelial cell proliferation and migration, favoring formation of new blood vessels and increasing permeability of existing blood vessels. Since bevacizumab, a recombinant humanized monoclonal antibody binding to all isoforms of VEGF, has been demonstrated to significantly improve survival in gynecologic cancer, some recent clinical research has explored the possibility of using novel therapies directed toward inhibition of angiogenesis in CC too. Here we review the main results from studies concerning the use of antiangiogenic drugs that are being investigated for the treatment of CC. PMID:25506227

Cluster of differentiation 146 (CD146) is an endothelial cell adhesion molecule which is overexpressed in various types of malignant cancer, including ovarian cancer. However, whether CD146 is overexpressed in another two types of gynecological cancer, cervicalcancer and endometrial cancer, remains unclear. In the present study, we showed that CD146 expression levels were higher in cells from cervicalcancer and endometrial cancer compared with their corresponding normal tissues, using anti-CD146 mouse antibody AA4 (mAb AA4) and that mAb AA4 exhibited a high performance for specificity, sensitivity and positive predictive value in the detection of these two types of cancer. CD146 expression was positively and significantly correlated with the pathological subtype of cervicalcancer and with the histological grade and depth of myometrial invasion in endometrial cancer. In addition, we confirmed that CD146 is present in the majority of blood vessels in cervical and endometrial cancer, suggesting that CD146 may be actively implicated in the metastasis of cervical and endometrial cancer via the vascular system. Thus, this study provides insights for further development of CD146 mAb in the detection of gynecological malignant cancer types and implies that a combined treatment strategy of anti-CD146 immunotherapy with other traditional chemo- or radiotherapy treatments may be a promising approach against cervical and endometrial cancer. PMID:23599761

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This study investigated the cytotoxicity of 55 species of plants. Each plant was rated as medicinal, or nonmedicinal based on the existing literature. About 79 % of the medicinal plants showed some cytotoxicity, while 75 % of the nonmedicinal plants showed bioactivity. It appears that Asteraceae, Labiatae, Pinaceae, and Chenopodiaceae were particularly active against human cervicalcancercells. Based on the literature, only three of the 55 plants have been significantly investigated for cytotoxicity. It is clear that there is much toxicological work yet to be done with both medicinal and nonmedicinal plants. 1.

Cervicalcancer remains a significant source of disease and death in Europe. However, we now have the means to prevent virtually every case of cervicalcancer through comprehensive, population-based, organised cervicalcancer prevention programmes that effectively integrate cervical screening with the new technologies and vaccines that are now available. Given the potential health benefits of these programmes in reducing disease incidence and mortality, their establishment is now an ethical imperative for all European countries. PMID:17598500

The optoelectronic method is one of the most promising concepts of biophysical program of the diagnostics of CIN and cervicalcancer. Objectives of the work are evaluation of sensitivity and specificity of the optoelectronic method in the detection of CIN and cervicalcancer. The paper shows correlation between the pNOR number and sensitivity/specificity of the optoelectronic method. The study included 293 patients with abnormal cervical cytology result and the following examinations: examination with the use of the optoelectronic method — Truscreen, colposcopic examination, and histopathologic biopsy. Specificity of the optoelectronic method for LGSIL was estimated at 65.70%, for HGSIL and squamous cell carcinoma of cervix amounted to 90.38%. Specificity of the optoelectronic method used to confirm lack of cervical pathology was estimated at 78.89%. The field under the ROC curve for the optoelectronic method was estimated at 0.88 (95% CI, 0.84-0.92) which shows high diagnostic value of the test in the detection of HGSIL and squamous cell carcinoma. The optoelectronic method is characterised by high usefulness in the detection of CIN, present in the squamous epithelium and squamous cell carcinoma of cervix.

Diallyl sulfide (DAS) is a component of garlic (Alliaceae family). Although diallyl polysulfide has been shown to exhibit anticancer activities, no report explored DAS-affected cell death in human cervicalcancercells in vitro. This study investigated DAS affected on cell-cycle regulation and apoptosis in human cervicalcancer Ca Ski cells. DAS at 25-100 ?M decreased the viability of Ca Ski cells by increasing G0/G1 phase arrest followed by induction of apoptosis in concentration- and time-dependent effects. Flow cytomteric assay indicated that DAS (75 ?M) promoted the production of Ca(2+) accumulation and decreased the level of mitochondrial membrane potential in Ca Ski cells. Western blotting showed that 75 ?M of DAS-induced G0/G1 phase arrest was mediated through the increased expression of p21, p27, and p53 with a simultaneous decrease in CDK2, CDK6, and CHK2 expression. The characteristics of apoptosis, such as morphological changes and DNA condensation, altered the ratio of Bax/Bcl-2 and sub-G1 phase occurred in Ca Ski cells after exposure to DAS. Furthermore, DAS induced mitochondrial dysfunction, leading to the release of cytochrome c for causing apoptosis in Ca Ski cells. These findings suggest that DAS might be a potential chemotherapeutic agent for the treatment of cervicalcancer. PMID:23530650

Background The aim of the study was to obtain stable radioresistant sub-lines from the human cervicalcancercell line HeLa by prolonged exposure to 252Cf neutron and X-rays. Radioresistance mechanisms were investigated in the resulting cells using microarray analysis of DNA damage repair genes. Methods HeLa cells were treated with fractionated 252Cf neutron and X-rays, with a cumulative dose of 75 Gy each, over 8 months, yielding the sub-lines HeLaNR and HeLaXR. Radioresistant characteristics were detected by clone formation assay, ultrastructural observations, cell doubling time, cell cycle distribution, and apoptosis assay. Gene expression patterns of the radioresistant sub-lines were studied through microarray analysis and verified by Western blotting and real-time PCR. Results The radioresistant sub-lines HeLaNR and HeLaXR were more radioresisitant to 252Cf neutron and X-rays than parental HeLa cells by detecting their radioresistant characteristics, respectively. Compared to HeLa cells, the expression of 24 genes was significantly altered by at least 2-fold in HeLaNR cells. Of these, 19 genes were up-regulated and 5 down-regulated. In HeLaXR cells, 41 genes were significantly altered by at least 2-fold; 38 genes were up-regulated and 3 down-regulated. Conclusions Chronic exposure of cells to ionizing radiation induces adaptive responses that enhance tolerance of ionizing radiation and allow investigations of cellular radioresistance mechanisms. The insights gained into the molecular mechanisms activated by these "radioresistance" genes will lead to new therapeutic targets for cervicalcancer. PMID:20184742

Cervicalcancer prevention requires a multipronged approach involving primary, secondary and tertiary prevention. The key element under primary prevention is human papilloma virus (HPV) vaccination. So far, only prophylactic HPV vaccines which prevent HPV infection by one or more subtypes are commercially available. Therapeutic HPV vaccines which aid in clearing established infection are still under trial. Secondary prevention entails early detection of precancerous lesions and its success is determined by the population coverage and the efficacy of the screening technique. A number of techniques are in use, including cytology, visual inspection (using the naked eye, magnivisualizer, acetic acid and Lugol's iodine), HPV testing and a combination of these methods. Updated screening guidelines have been advocated by the American Cancer Society in light of the role of HPV on cervical carcinogenesis. Recent research has also focussed on novel biomarkers that can predict progression to cancer in screen positive women and help to differentiate those who need treatment from those who can be left for follow-up. Last but not the least, effective treatment of precancerous lesions can help to reduce the incidence of invasive cervicalcancer and this constitutes tertiary prevention. A combination of these approaches can help to prevent the burden of cervicalcancer and its antecedent morbidity and mortality, but all of these are not feasible in all settings due to resource and allocation constraints. Thus, all countries, especially low and middle income ones, have to determine their own cocktail of approaches that work before we can say with certainty that yes, cervicalcancer can be prevented. PMID:25302177

Purpose: To identify women's sources of information about cervicalcancer screening, information which women report receiving during Pap consultations, information they would like to receive, and the relationships between perceived information needs, personal characteristics and information sources. Design/methodology/approach: Logistic regression…

Papillomaviruses infect a wide variety of animals, including humans. The human papillomavirus (HPV), in particular, is one of the most common causes of sexually transmitted disease. More than 200 types of HPV have been identified by DNA sequence data, and 85 HPV genotypes have been well characterized to date. HPV can infect the basal epithelial cells of the skin or inner tissue linings, and are, accordingly, categorized as either cutaneous or mucosal type. HPV is associated with a panoply of clinical conditions, ranging from innocuous lesions to cervicalcancer. In the early 1980s, studies first reported a link between cervicalcancer and genital HPV infection. Genital HPV infections are now recognized to be a major risk factor in at least 95% of cervicalcancers. 30 different HPV genotypes have been identified as causative of sexually transmitted diseases, most of which induce lesions in the cervix, vagina, vulva, penis, and anus, as the result of sexual contact. There is also direct evidence demonstrating that at least four of these genotypes are prerequisite factors in cervicalcancer. The main aim of this review was to evaluate the current literature regarding the pathovirology, diagnostics, vaccines, therapy, risk groups, and further therapeutic directions for HPV infections. In addition, we reviewed the current status of HPV infections in South Korean women, as evidenced by our data. PMID:15650698

Spontaneous preterm birth is a frequent complication of pregnancy and a common cause of morbidity in childhood. Obstetricians suspect abnormalities of the cervix are implicated in a significant number of preterm births. The cervix is composed of fibrous connective tissue and undergoes significant remodeling in preparation for birth. We hypothesized that a tissue engineering strategy could be used to develop three-dimensional cervical-like tissue constructs that would be suitable for investigating cervical remodeling. Cervicalcells were isolated from two premenopausal women undergoing hysterectomy for a benign gynecological condition, and the cells were seeded on porous silk scaffolds in the presence or absence of dynamic culture and with 10% or 20% serum. Morphological, biochemical, and mechanical properties were measured during the 8-week culture period. Cervicalcells proliferated in three-dimensions and synthesized an extracellular matrix with biochemical constituents and morphology similar to native tissue. Compared to static culture, dynamic culture was associated with significantly increased collagen deposition (p?0.05), sulfated glycosaminoglycan synthesis (p?0.05), and mechanical stiffness (p?0.05). Serum concentration did not affect measured variables. Relevant human tissue-engineered cervical-like constructs constitute a novel model system for a range of fundamental and applied studies related to cervical remodeling. PMID:20121593

The human ether à go-go 1 potassium channel (hEAG1) is required for cell cycle progression and proliferation of cancercells. Inhibitors of hEAG1 activity and expression represent potential therapeutic drugs in cancer. Previously, we have shown that hEAG1 expression is downregulated by calcitriol in a variety of cancercells. Herein, we provided evidence on the regulatory mechanism involved in such repressive effect in cells derived from human cervicalcancer. Our results indicate that repression by calcitriol occurs at the transcriptional level and involves a functional negative vitamin D response element (nVDRE) E-box type in the hEAG1 promoter. The described mechanism in this work implies that a protein complex formed by the vitamin D receptor-interacting repressor, the vitamin D receptor, the retinoid X receptor, and the Williams syndrome transcription factor interact with the nVDRE in the hEAG1 promoter in the absence of ligand. Interestingly, all of these transcription factors except the vitamin D receptor-interacting repressor are displaced from hEAG1 promoter in the presence of calcitriol. Our results provide novel mechanistic insights into calcitriol mode of action in repressing hEAG1 gene expression. PMID:25495694

Introduction: Cervicalcancer is the second leading cause of cancer morbidity and mortality for women around the world. Long non-coding RNAs (lncRNAs) have been investigated as a new class of regulators of cellular processes, such as cell growth, apoptosis, and carcinogenesis. Although downregulation of lncRNA GAS5 in several cancers has been studied, its role in cervicalcancer remains unknown. The aim of this study is to investigate the expression, clinical significance and biological role in cervicalcancer. Methods: Expression of GAS5 was analyzed in cervicalcancer tissues by quantitative Real-time PCR (qRT-PCR). And its association with overall survival of patients was analyzed by statistical analysis. Small interfering RNA (siRNA) was used to suppress GAS5 expression in cervicalcancercells. In vitro assays were performed to further explore the biological functions of GAS5 in cervicalcancer. Results: We found that GAS5 expression was markedly downregulated in cervicalcancer tissues than in corresponding adjacent normal tissues. Decreased GAS5 expression was significantly correlated with FIGO stage, vascular invasion and lymph node metastasis. Moreover, cervicalcancer patients with GAS5 lower expression have shown significantly poorer overall survival than those with higher GAS5 expression. And GAS5 expression was an independent prognostic marker of overall survival in a multivariate analysis. In vitro assays our data indicated that knockdown of GAS5 promoted cell proliferation, migration, and invasion. Conclusions: Our study presents that lncRNA GAS5 is a novel molecule involved in cervicalcancer progression, which provide a potential prognostic biomarker and therapeutic target. PMID:25400758

Absolute cancer risk is the probability that an individual with given risk factors and a given age will develop cancer over a defined period of time. Examples of these risk factors include race, age, sex, genetics, body mass index, family history of cancer, history of tobacco use, use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDS), physical activity, use of hormone replacement therapy, reproductive factors, history of cancer screening, and dietary factors.

The functions of many long non-coding RNAs (lncRNAs) in human cancers remain to be clarified. The lncRNA Hox transcript antisense intergenic RNA (HOTAIR) has been reported to reprogram chromatin organization and promote breast and colorectal cancer metastasis, the involvement of lncRNAs in cervicalcancer is just beginning to be studied. In the present study, we examined the expression and the functional role of HOTAIR in cervicalcancer. HOTAIR expression was determined in cervicalcancer tissues (n=111) and corresponding normal tissues (n=40) by using real-time polymerase chain reaction, and its correlation with clinical parameters and prognosis were analyzed. To determine the effect of HOTAIR knockdown and overexpression in cervicalcancercell lines, we used the CCK-8 assay, wound healing migration and matrigel invasion assay. The expression level of HOTAIR in cervicalcancer tissues was higher than that in corresponding non-cancerous tissues. High HOTAIR expression correlated with lymph node metastasis, and reduced overall survival. A multivariate analysis showed that HOTAIR was a prognostic factor for predicting cervicalcancer recurrence. Knockdown of HOTAIR reduced cell proliferation, migration, and invasion in cervicalcancercell lines. Moreover, HOTAIR regulated the expression of vascular endothelial growth factor, matrix metalloproteinase-9 and epithelial-to-mesenchymal transition (EMT)-related genes, which are important for cell motility and metastasis. Therefore, HOTAIR may promote tumor aggressiveness through the upregulation of VEGF and MMP-9 and EMT-related genes. These findings indicate that HOTAIR may represent a novel biomarker for predicting recurrence and prognosis and serve as a promising therapeutic target in cervicalcancer. PMID:25405331

The functions of many long non-coding RNAs (lncRNAs) in human cancers remain to be clarified. The lncRNA Hox transcript antisense intergenic RNA (HOTAIR) has been reported to reprogram chromatin organization and promote breast and colorectal cancer metastasis, the involvement of lncRNAs in cervicalcancer is just beginning to be studied. In the present study, we examined the expression and the functional role of HOTAIR in cervicalcancer. HOTAIR expression was determined in cervicalcancer tissues (n=111) and corresponding normal tissues (n=40) by using real-time polymerase chain reaction, and its correlation with clinical parameters and prognosis were analyzed. To determine the effect of HOTAIR knockdown and overexpression in cervicalcancercell lines, we used the CCK-8 assay, wound healing migration and Matrigel invasion assay. The expression level of HOTAIR in cervicalcancer tissues was higher than that in corresponding non-cancerous tissues. High HOTAIR expression correlated with lymph node metastasis, and reduced overall survival. A multivariate analysis showed that HOTAIR was a prognostic factor for predicting cervicalcancer recurrence. Knockdown of HOTAIR reduced cell proliferation, migration, and invasion in cervicalcancercell lines. Moreover, HOTAIR regulated the expression of vascular endothelial growth factor, matrix metalloproteinase-9 and epithelial-to-mesenchymal transition (EMT)-related genes, which are important for cell motility and metastasis. Therefore, HOTAIR may promote tumor aggressiveness through the upregulation of VEGF and MMP-9 and EMT-related genes. These findings indicate that HOTAIR may represent a novel biomarker for predicting recurrence and prognosis and serve as a promising therapeutic target in cervicalcancer. PMID:25405331

Cervicalcancer is the second largest cause of death among women worldwide. Nowadays, this disease is preventable and curable at low cost and low risk when an accurate diagnosis is done in due time, since it is the neoplasm with the highest prevention potential. This work describes the development of an expert system able to provide a diagnosis to cervical neoplasia (CN) precursor injuries through the integration of fuzzy logics and image interpretation techniques. The key contribution of this research focuses on atypical cases, specifically on atypical glandular cells (AGC). The expert system consists of 3 phases: (1) risk diagnosis which consists of the interpretation of a patient's clinical background and the risks for contracting CN according to specialists; (2) cytology images detection which consists of image interpretation (IM) and the Bethesda system for cytology interpretation, and (3) determination of cancer precursor injuries which consists of in retrieving the information from the prior phases and integrating the expert system by means of a fuzzy logics (FL) model. During the validation stage of the system, 21 already diagnosed cases were tested with a positive correlation in which 100% effectiveness was obtained. The main contribution of this work relies on the reduction of false positives and false negatives by providing a more accurate diagnosis for CN. PMID:23690881

Cervicalcancer is the second largest cause of death among women worldwide. Nowadays, this disease is preventable and curable at low cost and low risk when an accurate diagnosis is done in due time, since it is the neoplasm with the highest prevention potential. This work describes the development of an expert system able to provide a diagnosis to cervical neoplasia (CN) precursor injuries through the integration of fuzzy logics and image interpretation techniques. The key contribution of this research focuses on atypical cases, specifically on atypical glandular cells (AGC). The expert system consists of 3 phases: (1) risk diagnosis which consists of the interpretation of a patient's clinical background and the risks for contracting CN according to specialists; (2) cytology images detection which consists of image interpretation (IM) and the Bethesda system for cytology interpretation, and (3) determination of cancer precursor injuries which consists of in retrieving the information from the prior phases and integrating the expert system by means of a fuzzy logics (FL) model. During the validation stage of the system, 21 already diagnosed cases were tested with a positive correlation in which 100% effectiveness was obtained. The main contribution of this work relies on the reduction of false positives and false negatives by providing a more accurate diagnosis for CN. PMID:23690881

Summary The expression of N-myc down-regulated gene 1 (NDRG1) has previously been reported to be involved in the proliferation, differentiation,\\u000a invasion and metastasis of cancercells, but its role in cervicalcancer is still unclear. This study aimed to investigate\\u000a the expression of NDRG1gene in human cervicalcancer and its effect on aggressive tumor behaviors. The NDRG1 expression in\\u000a cervical tissues

Cervicalcancer is the third most common cancer affecting women worldwide. It is characterized by chromosomal aberrations and alteration in the expression levels of many cell cycle regulatory proteins, driven primarily by transforming human papillomavirus (HPV) infection. MYBL2 is a member of the MYB proto-oncogene family that encodes DNA binding proteins. These proteins are involved in cell proliferation and control of cellular differentiation. We have previously demonstrated the utility of MYBL2 as a putative biomarker for cervical pre-cancer and cancer. In this chapter we describe the methodological approach for testing MYBL2 protein expression in tissue biopsies from cases of cervical intraepithelial neoplasia (CIN) and cervicalcancer, using immunohistochemistry techniques on the automated immunostaining platform, the Ventana BenchMark LT. The protocol outlines the various steps in the procedure from cutting tissue sections, antibody optimization, antigen retrieval, immunostaining, and histological review. PMID:25348311

Marine invertebrates called ascidians are prolific producers of bioactive substances. The ascidian Eudistoma viride, distributed along the Southeast coast of India, was investigated for its in vitro cytotoxic activity against human cervical carcinoma (HeLa) cells by the MTT assay. The crude methanolic extract of E. viride, with an IC50 of 53 ?g/ml, was dose-dependently cytotoxic. It was more potent at 100 ?g/ml than cyclohexamide (1 ?g/ml), reducing cell viability to 9.2%. Among nine fractions separated by chromatography, ECF-8 exhibited prominent cytoxic activity at 10 ?g/ml. The HPLC fraction EHF-21 of ECF-8 was remarkably dose- and time-dependently cytotoxic, with 39.8% viable cells at 1 ?g/ml compared to 51% in cyclohexamide-treated cells at the same concentration; the IC50 was 0.49 ?g/ml. Hoechst staining of HeLa cells treated with EHF-21 at 0.5 ?g/ml revealed apoptotic events such an cell shrinkage, membrane blebbing, chromatin condensation and formation of apoptotic bodies. Cell size and granularity study showed changes in light scatter, indicating the characteristic feature of cells dying by apoptosis. The cell-cycle analysis of HeLa cells treated with fraction EHF-21 at 1 ?g/ml showed the marked arrest of cells in G0/G1, S and G2/M phases and an increase in the sub G0/G1 population indicated an increase in the apoptotic cell population. The statistical analysis of the sub-G1 region showed a dose-dependent induction of apoptosis. DNA fragmentation was also observed in HeLa cells treated with EHF-21. The active EHF-21 fraction, a brominated indole alkaloid Eudistomin H, led to apoptotic death of HeLa cells. PMID:25550562

...Disease Control and Prevention Breast and CervicalCancer Early Detection and Control...detection and control of breast and cervicalcancer. The committee makes recommendations...Task Force guidelines for breast and cervicalcancer screening; Impact of...

...Disease Control and Prevention Breast and CervicalCancer Early Detection and Control...aforementioned committee: Name: Breast and CervicalCancer Early Detection and Control...detection and control of breast and cervicalcancer. The committee makes...

...Disease Control and Prevention Breast and CervicalCancer Early Detection and Control...detection and control of breast and cervicalcancer. The committee makes recommendations...Reform and its impact for breast and cervicalcancer screening; updates on...

As iron ions may participate in the pathogenesis of cancer and viral infections, the aim of this study was to monitor their influence on proliferation, E6 and E7 oncogene expression and reactive oxygen species (ROS) production in two human papilloma virus (HPV) positive cervical carcinoma cell lines (HeLa and SiHa) and one HPV negative vulvar cell line (A431). The anti-anaemic drug, ferric-sorbitol-citric acid complex (FSC) as a source of Fe(III) ions was used. Cells were treated with FSC at the concentrations between 0.001 and 1 mM Fe(III) for different time periods. Fe(III) ions inhibited the viability of HeLa and A431 cells while it had no influence on SiHa cells. Furthermore, Fe(III) treatment showed a time-dependent and a higher stimulatory effect on E6/E7 expression in SiHa cells than in HeLa cells. Fe(III) ion treatment with concentrations lower than 0.1mM showed a time and a concentration dependent intracellular ROS production in all tested cell lines, while the treatment with 1mM concentration decreased ROS production in all tested cell lines. In conclusion, Fe(III) ion treatment apart from having an anti-tumour effect, as we previously described, enhances survival of HPV 16-positive cells and might be associated with HPV oncogenesis. PMID:21044880

Cervicalcancer ranks high among the causes of female cancer mortalities and is an important disease in developing and developed countries. Current diagnosis of cervicalcancer depends on colposcopy, pathological diagnosis and preoperative diagnosis using methods, including magnetic resonance imaging and computed tomography. Advanced cervicalcancer has a poor prognosis. The tumor marker squamous cell carcinoma is conventionally used for screening, but recent studies have revealed the mechanisms of carcinogenesis and the factors associated with a poor prognosis in cervicalcancer. These include epigenetic biomarkers, with the methylation level of the checkpoint with forkhead and ring finger gene being potentially useful for predicting the malignancy of cervicalcancer and sensitivity to treatment with paclitaxel. The extent of methylation of the Werner DNA helicase gene is also useful for determining sensitivity to an anticancer agent, CPT-11. In addition to epigenetic changes, the expression levels of hypoxia-inducible factor 1? subunit, epidermal growth factor receptor and cyclooxygenase-2 have been reported as possible biomarkers in cervicalcancer. Novel prognostic factors, including angiogenic factors, fragile histidine triad, thymidylate synthase, glucose-related protein 58 and mucin antigens, have also been described, and hemoglobin and platelets may also be significant prognostic biomarkers. Utilization of these biomarkers may facilitate personalized treatment and improved outcomes in cervicalcancer. PMID:25054026

Fisetin (3,3’,4’,7-tetrahydroxyflavone), a naturally occurring flavonoid, has been reported to inhibit proliferation and induce apoptosis in several cancer types. However, its effect on the anti-metastatic potential of cervicalcancercells remains unclear. In the present study, we found that fisetin inhibits the invasion and migration of cervicalcancercells. The expression and activity of urokinase plasminogen activator (uPA) was significantly suppressed by fisetin in a dose-dependent manner. We also demonstrated that fisetin reduces the phosphorylation of p38 MAPK, but not that of ERK1/2, JNK1/2, or AKT. Addition of a p38 MAPK inhibitor, SB203580, further enhanced the inhibitory effect of fisetin on the expression and activity of uPA and the invasion and motility in cervicalcancercells. Fisetin suppressed the TPA (tetradecanoylphorbol-13-acetate)-induced activation of p38 MAPK and uPA, and inhibited the TPA-enhanced migratory and invasive abilities. Furthermore, the promoter activity of the uPA gene was dramatically repressed by fisetin, which disrupted the nuclear translocation of NF-?B and its binding amount on the promoter of the uPA gene, and these suppressive effects could be further enhanced by SB203580. This study provides strong evidence for the molecular mechanism of fisetin in inhibiting the aggressive phenotypes by repression of uPA via interruption of p38 MAPK-dependent NF-?B signaling pathway in cervicalcancercells and thus contributes insight to the potential of using fisetin as a therapeutic strategy against cervicalcancer by inhibiting migration and invasion. PMID:23940799

Fisetin (3,3',4',7-tetrahydroxyflavone), a naturally occurring flavonoid, has been reported to inhibit proliferation and induce apoptosis in several cancer types. However, its effect on the anti-metastatic potential of cervicalcancercells remains unclear. In the present study, we found that fisetin inhibits the invasion and migration of cervicalcancercells. The expression and activity of urokinase plasminogen activator (uPA) was significantly suppressed by fisetin in a dose-dependent manner. We also demonstrated that fisetin reduces the phosphorylation of p38 MAPK, but not that of ERK1/2, JNK1/2, or AKT. Addition of a p38 MAPK inhibitor, SB203580, further enhanced the inhibitory effect of fisetin on the expression and activity of uPA and the invasion and motility in cervicalcancercells. Fisetin suppressed the TPA (tetradecanoylphorbol-13-acetate)-induced activation of p38 MAPK and uPA, and inhibited the TPA-enhanced migratory and invasive abilities. Furthermore, the promoter activity of the uPA gene was dramatically repressed by fisetin, which disrupted the nuclear translocation of NF-?B and its binding amount on the promoter of the uPA gene, and these suppressive effects could be further enhanced by SB203580. This study provides strong evidence for the molecular mechanism of fisetin in inhibiting the aggressive phenotypes by repression of uPA via interruption of p38 MAPK-dependent NF-?B signaling pathway in cervicalcancercells and thus contributes insight to the potential of using fisetin as a therapeutic strategy against cervicalcancer by inhibiting migration and invasion. PMID:23940799

A female with main clinical manifestation of postcoital vaginal bleeding presented to our hospital. The patient was initially diagnosed with cervical carcinoma by the clinicians of the local hospital. However, the biopsy of the cervical lesions revealed chronic inflammation and erosion of cervical mucosa. And the rapid plasma reagin ratio is 1:256. Finally, the patient was diagnosed with syphilitic cervicitis and treated with minocycline 0.1gram twice a day. The patient was cured after the treatment. PMID:25486010

Human papillomavirus (HPV) is one of the most widely publicized and researched pathogenic DNA viruses. For decades, HPV research has focused on transforming viral activities in cervicalcancer. During the past 15 years, however, HPV has also emerged as a major etiological agent in cancers of the head and neck, in particular squamous cell carcinoma. Even with significant strides achieved towards the screening and treatment of cervicalcancer, and preventive vaccines, cervicalcancer remains the leading cause of cancer-associated deaths for women in developing countries. Furthermore, routine screens are not available for those at risk of head and neck cancer. The current expectation is that HPV vaccination will prevent not only cervical, but also head and neck cancers. In order to determine if previous cervicalcancer models for HPV infection and transformation are directly applicable to head and neck cancer, clinical and molecular disease aspects must be carefully compared. In this review, we briefly discuss the cervical and head and neck cancer literature to highlight clinical and genomic commonalities. Differences in prognosis, staging and treatment, as well as comparisons of mutational profiles, viral integration patterns, and alterations in gene expression will be addressed. PMID:25226287

Although human papillomavirus (HPV) infection has been found in most of the cervicalcancer cases, additional genetic and epigenetic changes are required for disease progression. Previously, it was thought that only genetic mutation plays a key role in cervicalcancer development. But recent advances in the biology of cervicalcancer revealed that epigenetic alteration is common in cervical carcinogenesis and metastasis. Epigenetic alteration due to aberrant DNA methylation and histone modification has been extensively studied in cervicalcancer. Recent research strategies keep insight into noncoding RNAs, especially miRNA and lncRNA. At the same time, interest has been grown to study the utility of these changes as biomarkers to determine disease progression as well as use them as the therapeutic targets. This study has been aimed to review the recent progress of epigenetic study for cervicalcancer research including role of these epigenetic changes in disease progression, their prognostic values, and their use in targeted therapy. PMID:24554414

We previously reported frequent loss of microRNA-218 (miR-218) in cervicalcancer, which was associated with tumor progression and poor prognosis. As microRNAs were found invovled in the regulation of radiosensitivity in various human cancers, we therefore aim to investigate the effects of miR-218 on radiosensitivity of cervicalcancer in the present study. The clonogenic survival assay demonstrated that loss of miR-218 could predict radioresistance in the primary cervicalcancercells (R2=0.6516, P<0.001). In vitro, abundant miR-218 increased the radiosensitivity in cervicalcancercells (P<0.001 for HeLa, P=0.009 for SiHa, P=0.016 for C33A and P=0.01 for CaSki). Upregulation of miR-218 significantly enhanced the radiation-induced apoptosis, which was further enhanced by the combination of miR-218 overexpression and radiation In xenograft growth assay, combination of miR-218 overexpression and radiation notably induced cellular apoptosis and suppressed tumor growth. In conclusion, we demonstrated that miR-218 resensitized cervicalcancercells to radiation via promoting cellular apoptosis. Moreover, we proved that miR-218 as a potent predictor of radiosensitivity in cervicalcancer, especially for those patients with loss of miR-218. PMID:24843318

... the PDQ summary on Unusual Cancers of Childhood . Human papillomavirus (HPV) infection is the major risk factor ... be at risk. Infection of the cervix with human papillomavirus (HPV) is almost always the cause of ...

DNA methylation is important in cancer development and is a promising biomarker for cancer detection. An epigenomic approach used in our previous work showed that LMX-1A is methylation-silenced in cervicalcancer. LMX-1A, a LIM-homeobox gene, is known to participate in developmental events; however, there are at present no data on the role of LMX-1A in cancers. In this study, we characterized the function of this transcription factor by examining cell lines, animal models and human cervical neoplastic tissues, and found that over-expression of LMX-1A does not affect cell proliferation or the cell cycle of cervicalcancercell lines but significantly inhibits colony formation and invasion in vitro. Analysis of changes in epithelial-mesenchymal transition (EMT) markers, such as CDH1, CDH2, VIMENTIN, SNAIL, SLUG and TWIST, revealed involvement of the EMT in LMX-1A-mediated cancer invasion; this result was validated in a stable transfectant over-expressing LMX-1A with RNA interference. Xenograft studies using immunocompromised mice confirmed the suppressor effects of LMX-1A on tumour formation and distant metastasis in cervicalcancercell lines. LMX-1A immunohistochemical staining of tissue arrays containing the full spectrum of cervical neoplasms, including normal cervix, low-grade cervical intra-epithelial neoplasia (CIN), high-grade CIN, locally invasive and distant metastatic cancers, demonstrated the critical role of LMX-1A in invasion and metastasis. Furthermore, we found by analysing TGFbeta-BMP signalling that BMP4 and BMP6 are down-regulated by LMX-1A. The results of this study suggest that LMX-1A suppresses cancer invasion and metastasis in cervicalcancer through an incomplete EMT. PMID:19644956

Expression of the bovine papillomavirus E2 regulatory protein in human cervical carcinoma cell lines repressed expression of the resident human papillomavirus E6 and E7 oncogenes and within a few days caused essentially all of the cells to synchronously display numerous phenotypic markers characteristic of cells undergoing replicative senescence. This process was accompanied by marked but in some cases transient alterations in the expression of cell cycle regulatory proteins and by decreased telomerase activity. We propose that the human papillomavirus E6 and E7 proteins actively prevent senescence from occurring in cervical carcinoma cells, and that once viral oncogene expression is extinguished, the senescence program is rapidly executed. Activation of endogenous senescence pathways in cancercells may represent an alternative approach to treat human cancers.

BACKGROUND: Exfoliated cervicalcells are used in cytology-based cancer screening and may also be a source for molecular biomarkers indicative of neoplastic changes in the underlying tissue. However, because of keratinization and terminal differentiation it is not clear that these cells have an mRNA profile representative of cervical tissue, and that the profile can distinguish the lesions targeted for early

Purpose: The aim of this study was to evaluate efficacy of gynecologic examination under general anesthesia with cervical biopsies after (chemo) radiation for cervicalcancer to identify patients with residual disease who may benefit from salvage surgery. Methods and Materials: In a retrospective cohort study data of all cervicalcancer patients with the International Federation of Gynecology and Obstetrics (FIGO) Stage IB1 to IVA treated with (chemo) radiation between 1994 and 2001 were analyzed. Patients underwent gynecologic examination under anesthesia 8 to 10 weeks after completion of treatment. Cervical biopsy samples were taken from patients judged to be operable. In case of residual cancer, salvage surgery was performed. Results: Between 1994 and 2001, 169 consecutive cervicalcancer patients received primary (chemo) radiation, of whom 4 were lost to follow-up. Median age was 56 years (interquartile range [IQR], 44-71) and median follow-up was 3.5 years (IQR, 1.5-5.9). In each of 111 patients a biopsy sample was taken, of which 90 (81%) showed no residual tumor. Vital tumor cells were found in 21 of 111 patients (19%). Salvage surgery was performed in 13 of 21 (62%) patients; of these patients, 5 (38%) achieved long-term, complete remission after salvage surgery (median follow-up, 5.2 years; range, 3.9-8.8 years). All patients with residual disease who did not undergo operation (8/21) died of progressive disease. Locoregional control was more often obtained in patients who underwent operation (7 of 13) than in patients who were not selected for salvage surgery (0 of 8 patients) (p < 0.05). Conclusions: Gynecologic examination under anesthesia 8 to 10 weeks after (chemo) radiation with cervical biopsies allows identification of those cervicalcancer patients who have residual local disease, of whom a small but significant proportion may be salvaged by surgery.

Cervicalcancer is the third most common cancer in women worldwide; definitive radiation therapy and concurrent chemotherapy is the accepted standard of care for patients with node positive or locally advanced tumors > 4 cm. Brachytherapy is an important part of definitive radiotherapy shown to improve overall survival. While results for two-dimensional X-ray based brachytherapy have been good in terms of local control especially for early stage disease, unexplained toxicities and treatment failures remain. Improvements in brachytherapy planning have more recently paved the way for three-dimensional image-based brachytherapy with volumetric optimization which increases tumor control, reduces toxicity, and helps predict outcomes. Advantages of image-based brachytherapy include: improved tumor coverage (especially for large volume disease), decreased dose to critical organs (especially for small cervix), confirmation of applicator placement, and accounting for sigmoid colon dose. A number of modalities for image-based brachytherapy have emerged including: magnetic resonance imaging (MRI), computed tomography (CT), CT-MRI hybrid, and ultrasound with respective benefits and outcomes data. For practical application of image-based brachytherapy the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology Working Group and American Brachytherapy Society working group guideline serve as invaluable tools, additionally here-in we outline our institutional clinical integration of these guidelines. While the body of literature supporting image-based brachytherapy continues to evolve a number of uncertainties and challenges remain including: applicator reconstruction, increasing resource/cost demands, mobile four-dimensional targets and organs-at-risk, and accurate contouring of “grey zones” to avoid marginal miss. Ongoing studies, including the prospective EMBRACE (an international study of MRI-guided brachytherapy in locally advanced cervicalcancer) trial, along with continued improvements in imaging, contouring, quality assurance, physics, and brachytherapy delivery promise to perpetuate the advancement of image-based brachytherapy to optimize outcomes for cervicalcancer patients. PMID:25493230

Cervicalcancer is the third most common cancer in women worldwide; definitive radiation therapy and concurrent chemotherapy is the accepted standard of care for patients with node positive or locally advanced tumors > 4 cm. Brachytherapy is an important part of definitive radiotherapy shown to improve overall survival. While results for two-dimensional X-ray based brachytherapy have been good in terms of local control especially for early stage disease, unexplained toxicities and treatment failures remain. Improvements in brachytherapy planning have more recently paved the way for three-dimensional image-based brachytherapy with volumetric optimization which increases tumor control, reduces toxicity, and helps predict outcomes. Advantages of image-based brachytherapy include: improved tumor coverage (especially for large volume disease), decreased dose to critical organs (especially for small cervix), confirmation of applicator placement, and accounting for sigmoid colon dose. A number of modalities for image-based brachytherapy have emerged including: magnetic resonance imaging (MRI), computed tomography (CT), CT-MRI hybrid, and ultrasound with respective benefits and outcomes data. For practical application of image-based brachytherapy the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology Working Group and American Brachytherapy Society working group guideline serve as invaluable tools, additionally here-in we outline our institutional clinical integration of these guidelines. While the body of literature supporting image-based brachytherapy continues to evolve a number of uncertainties and challenges remain including: applicator reconstruction, increasing resource/cost demands, mobile four-dimensional targets and organs-at-risk, and accurate contouring of "grey zones" to avoid marginal miss. Ongoing studies, including the prospective EMBRACE (an international study of MRI-guided brachytherapy in locally advanced cervicalcancer) trial, along with continued improvements in imaging, contouring, quality assurance, physics, and brachytherapy delivery promise to perpetuate the advancement of image-based brachytherapy to optimize outcomes for cervicalcancer patients. PMID:25493230

Cervicalcancer is the third most common cancer in women worldwide, leading to about 300,000 deaths each year. Most cervicalcancers are caused by human papillomavirus (HPV) infection. However, persistent transcriptional activity of HPV oncogenes, which indicates active roles of HPV in cervicalcancer maintenance and progression, has not been well characterized. Using our recently developed assays for comprehensive profiling of HPV E6/E7 transcripts, we have detected transcriptional activities of 10 high-risk HPV strains from 87 of the 101 cervical tumors included in the analysis. These HPV-positive patients had significantly better survival outcome compared with HPV-negative patients, indicating HPV transcriptional activity as a favorable prognostic marker for cervicalcancer. Furthermore, we have determined microRNA (miRNA) expression changes that were correlated with tumor HPV status. Our profiling and functional analyses identified miR-9 as the most activated miRNA by HPV E6 in a p53-independent manner. Further target validation and functional studies showed that HPV-induced miR-9 activation led to significantly increased cell motility by downregulating multiple gene targets involved in cell migration. Thus, our work helps to understand the molecular mechanisms as well as identify potential therapeutic targets for cervicalcancer and other HPV-induced cancers. PMID:25344913

Thymoquinone (TQ) has been shown to exhibit antitumor properties. Thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) was developed to improve the bioavailability and cytotoxicity of TQ. This study was conducted to determine the cytotoxic effects of TQ-NLC on breast cancer (MDA-MB-231 and MCF-7) and cervicalcancercell lines (HeLa and SiHa). TQ-NLC was prepared by applying the hot high pressure homogenization technique. The mean particle size of TQ-NLC was 35.66 ± 0.1235?nm with a narrow polydispersity index (PDI) lower than 0.25. The zeta potential of TQ-NLC was greater than ?30?mV. Polysorbate 80 helps to increase the stability of TQ-NLC. Differential scanning calorimetry showed that TQ-NLC has a melting point of 56.73°C, which is lower than that of the bulk material. The encapsulation efficiency of TQ in TQ-NLC was 97.63 ± 0.1798% as determined by HPLC analysis. TQ-NLC exhibited antiproliferative activity towards all the cell lines in a dose-dependent manner which was most cytotoxic towards MDA-MB-231 cells. Cell shrinkage was noted following treatment of MDA-MB-231 cells with TQ-NLC with an increase of apoptotic cell population (P < 0.05). TQ-NLC also induced cell cycle arrest. TQ-NLC was most cytotoxic towards MDA-MB-231 cells. It induced apoptosis and cell cycle arrest in the cells. PMID:25632388

Background: Understanding how "health issues" are socially constructed may be useful for creating culturally relevant programs for Hispanic/Latino populations. Purpose: We explored the constructed meanings of cervicalcancer and cervicalcancer screening among Panamanian women, as well as socio-cultural factors that deter or encourage screening…

Since 1976 a clinical trial has been conducted to test the feasibility, the potential, and to develop methods for using the neutron-emitting radioactive isotope, californium-252 (Cf-252), for the treatment of cervicalcancer. A total of 218 patients were treated in the initial study period from 1976 until 1983. The trials initially treated advanced cervicalcancer patients using different doses and

The goals of any cervicalcancer prevention program should be threefold: to achieve high coverage of the population at risk, to screen women with an accurate test as part of high-quality services, and to ensure that women with positive test results are properly managed. This article focuses on the experiences of the Alliance for CervicalCancer Prevention (ACCP) in delivery

In order to assess any correlation between cervicalcancer and age at marriage and childbearing, matched control groups were formed. From the comparison it appears that cervicalcancer patients are more likely to be married and to have married at an earlier age than control women. In the same age groups at marriage there was no difference in the number of children between the cervicalcancer patients and the control women. It appeared that cervicalcancer patients had their first child earlier than control women. There were more illegitimate children in the cervicalcancer groups than in the control groups, but after the wedding date there were no differences between the cervicalcancer groups and the control groups in the time between the wedding date and the date of birth of the first child. The data show that after pregnancy or childbirth, in particular at an early age, there is a greater risk of getting a cervicalcancer. By contrast, nulliparous married women seem to have a low risk of cervicalcancer. PMID:264057

Synaptonemal complex protein 3 (SCP3), a member of Cor1 family, is up-regulated in various cancercells; however, its oncogenic potential and clinical significance has not yet been characterized. In the present study, we investigated the oncogenic role of SCP3 and its relationship with phosphorylated AKT (pAKT) in cervical neoplasias. The functional role of SCP3 expression was investigated by overexpression or knockdown of SCP3 in murine cell line NIH3T3 and human cervicalcancercell lines CUMC6, SiHa, CaSki, and HeLa both in vitro and in vivo. Furthermore, we examined SCP3 expression in tumor specimens from 181 cervicalcancer and 400 cervical intraepithelial neoplasia (CIN) patients by immunohistochemistry and analyzed the correlation between SCP3 expression and clinicopathologic factors or survival. Overexpression of SCP3 promoted AKT-mediated tumorigenesis both in vitro and in vivo. Functional studies using NIH3T3 cells demonstrated that the C-terminal region of human SCP3 is important for AKT activation and its oncogenic potential. High expression of SCP3 was significantly associated with tumor stage (P?=?0.002) and tumor grade (P<0.001), while SCP3 expression was positively associated with pAKT protein level in cervical neoplasias. Survival times for patients with cervicalcancer overexpressing both SCP3 and pAKT (median, 134.0 months, n?=?68) were significantly shorter than for patients with low expression of either SCP3 or pAKT (161.5 months, n?=?108) as determined by multivariate analysis (P?=?0.020). Our findings suggest that SCP3 plays an important role in the progression of cervicalcancer through the AKT signaling pathway, supporting the possibility that SCP3 may be a promising novel cancer target for cervicalcancer therapy. PMID:24905095

Cervicovaginal cytology, known as Pap smear, is the most effective screening test in medical oncology. Introduced by Dr. George Papanicolaou in 1940, the Pap smear is now being recognized as a major contributor to the remarkable decrease in cervicalcancer morbidity and mortality among women throughout the world. However, there are still significant numbers of women who lose their lives to cervicalcancer every day. To overcome this major problem, first, we must search for the reasons for these lost lives and then take appropriate measures to resolve the existing issues. There is now substantial evidence that emphasizes the importance of an effective screening program. This program must integrate education and accessibility to health care for all women regardless of age, race, ethnic background and socioeconomic status. The public, the media, the government and health care providers must also become acutely aware of the inherent difficulties involved in providing a high-quality Pap smear. Compounded by medicolegal pressures and reimbursement issues, the Pap smear has become one of the more difficult tests to perform. Current reimbursement mechanisms are not appropriate for the cost of providing the service and cannot guarantee the resources necessary for a high-quality Pap smear. Congress should consider mandating direct billing to the patient for the service, so that cervicovaginal cytology could be reimbursed on a level commensurate with the requirements of providing quality service. A concerted effort should also be made to enhance the level of public knowledge about the issues surrounding Pap smear. This could be achieved by fostering the idea of designating a "CervicalCancer Awareness Month," and by encouraging the spirit of community networking. PMID:9379163

Virus-like particles (VLPs) of human papillomavirus (HPV) are used as a vaccine against HPV-induced cancer, and recently we have shown that these VLPs are able to activate natural killer (NK) cells. Since NK cells collaborate with dendritic cells (DCs) to induce an immune response against viral infections and tumors, we studied the impact of this crosstalk in the context of HPV vaccination. NK cells in the presence of HPV-VLPs enhanced DC-maturation as shown by an upregulation of CD86 and HLA-DR and an increased production of IL-12p70, but not of the immunosuppressive cytokine IL-10. This activation was bidirectional. Indeed, in the presence of HPV-VLPs, DCs further activated NK cells by inducing the upregulation of cell surface activation markers (CD69 and HLA-DR). The function of NK cells was also improved as shown by an increase in IFN-? secretion and cytotoxic activity against an HPV(+) cell line. This crosstalk between NK cells and DCs needed CD40 interaction and IL-12p70 secretion, whereas NKG2D was not implicated. Our results provide insight into how VLPs interact with innate immune cells and how NK cells and DCs play a role in the immune response induced by this vaccine agent. PMID:25229656

Apoptosis induction by short hairpin RNA (shRNA) expression vectors could be an efficient and promising strategy for cancer gene therapy. Ultrasound-targeted microbubble destruction (UTMD) is an appealing technique. In this study, we investigated the apoptosis induction and suppression of cell proliferation in vivo transfected by the UTMD-based shRNA delivery system. Nude mice with transplanted tumors of cervicalcancer were randomly arranged into three groups: control group, plasmid injection and ultrasound (P + US), P + UTMD group. Expressions of Survivin and proliferating cell nuclear antigen (PCNA), Bcl-2, Bax, Caspase-3, Ki-67, nucleostemin (NS) were investigated by immunohistochemistry. Furthermore, microvessel density (MVD) was detected by CD34 protein expressions and apoptotic index (AI) was measured by TUNEL. As compared with those in the control and P + US groups, protein expressions of PCNA, Ki-67, Bcl-2, Survivin and NS in P + UTMD groups were down-regulated markedly, while those of Bax, Caspase-3 were up-regulated significantly (p < 0.05). MVD decreased significantly, whereas AI increased remarkably (p < 0.05). We suggested that UTMD-based shRNA delivery system could induce apoptosis and inhibit proliferation significantly, without causing any apparently adverse effect, representing a new, promising technology that would be used in the future gene therapy and research. PMID:23325045

Patients with advanced stage or recurrent cervicalcancer represent a population with limited chemotherapeutic options. More specifically, patients with recurrent disease have a poor salvage rate, with a 5-year survival rate of less than 10%. This year, the first prospective phase III clinical trial exploring the anti-angiogenic agent, bevacizumab, was published, meeting its primary endpoint, with a significant improvement in overall survival. As such, a review of anti-angiogenic therapy in the treatment of this disease is warranted. PMID:25364393

We have previously localized a cervicalcancer tumor suppressor gene to a 300 kb interval of 11q13. Analysis of candidate genes revealed loss of expression of cystatin E/M, a lysosomal cysteine protease inhibitor, in 6 cervicalcancercell lines and 9 of 11 primary cervical tumors. Examination of the three exons in four cervicalcancercell lines, 19 primary tumors, and 21 normal controls revealed homozygous deletion of exon 1 sequences in one tumor. Point mutations were observed in six other tumors. Two tumors contained mutations at the consensus binding sites for cathepsin L, a lysosomal protease over-expressed in cervicalcancer. Introduction of these two point mutations using site directed mutagenesis resulted in reduced binding of mutated cystatin E/M to cathepsin L. Although mutations were not observed in any cell lines, four cell lines and 12 of 18 tumors contained promoter hypermethylation. Re-expression of cystatin E/M was observed after 5?aza 2-deoxycytidiene and/or Trichostatin A treatment of cervicalcancercell lines, HeLa and SiHa, confirming promoter hypermethylation. Ectopic expression of cystatin E/M in these two cell lines resulted in growth suppression. There was also suppression of soft agar colony formation by HeLa cells expressing the cystatin E/M gene. Re-expression of cystatin E/M resulted in decreased intracellular and extracellular expression of cathepsin L. Over-expression of cathepsin L resulted in increased cell growth which was inhibited by the reintroduction of cystatin E/M. We conclude, therefore, that cystatin E/M is a cervicalcancer suppressor gene and that the gene is inactivated by somatic mutations and promoter hypermethylation. PMID:18506750

Abstract Background Vietnamese American women represent one of the ethnic subgroups at great risk for cervicalcancer in the United States. The underutilization of cervicalcancer screening and the vulnerability of Vietnamese American women to cervicalcancer may be compounded by their health beliefs. Objective The objective of this study was to explore the associations between factors of the Health Belief Model (HBM) and cervicalcancer screening among Vietnamese American women. Methods Vietnamese American women (n=1,450) were enrolled into the randomized controlled trial (RCT) study who were recruited from 30 Vietnamese community-based organizations located in Pennsylvania and New Jersey. Participants completed baseline assessments of demographic and acculturation variables, health care access factors, and constructs of the HBM, as well as health behaviors in either English or Vietnamese. Results The rate of those who had ever undergone cervicalcancer screening was 53% (769/1450) among the participants. After adjusting for sociodemographic variables, the significant associated factors from HBM included: believing themselves at risk and more likely than average women to get cervicalcancer; believing that cervicalcancer changes life; believing a Pap test is important for staying healthy, not understanding what is done during a Pap test, being scared to know having cervicalcancer; taking a Pap test is embarrassing; not being available by doctors at convenient times; having too much time for a test; believing no need for a Pap test when feeling well; and being confident in getting a test. Conclusion Understanding how health beliefs may be associated with cervicalcancer screening among underserved Vietnamese American women is essential for identifying the subgroup of women who are most at risk for cervicalcancer and would benefit from intervention programs to increase screening rates. PMID:23428284

Cervicalcancer is the leading cause of cancer mortality in India, accounting for 17% of all cancer deaths among women aged 30 to 69 years. At current incidence rates, the annual burden of new cases in India is projected to increase to 225,000 by 2025, but there are few large-scale, organized cervicalcancer prevention programs in the country. We conducted a review of the cervicalcancer prevention research literature and programmatic experiences in India to summarize the current state of knowledge and practices and recommend research priorities to address the gap in services. We found that research and programs in India have demonstrated the feasibility and acceptability of cervicalcancer prevention efforts and that screening strategies requiring minimal additional human resources and laboratory infrastructure can reduce morbidity and mortality. However, additional evidence generated through implementation science research is needed to ensure that cervicalcancer prevention efforts have the desired impact and are cost-effective. Specifically, implementation science research is needed to understand individual- and community-level barriers to screening and diagnostic and treatment services; to improve health care worker performance; to strengthen links among screening, diagnosis, and treatment; and to determine optimal program design, outcomes, and costs. With a quarter of the global burden of cervicalcancer in India, there is no better time than now to translate research findings to practice. Implementation science can help ensure that investments in cervicalcancer prevention and control result in the greatest impact. PMID:24217555

The incidence of cervicalcancer in the United States has decreased more than 50% in the past 30 years because of widespread screening with cervical cytology. In 1975, the rate was 14.8 per 100,000 women. By 2008, it had been reduced to 6.6 per 100,000 women. Mortality from the disease has undergone a similar decrease from 5.55 per 100,000 women in 1975 to 2.38 per 100,000 women in 2008 (1). The American Cancer Society (ACS) estimates that there will be 12,170 new cases of cervicalcancer in the United States in 2012, with 4,220 deaths from the disease (2). Cervicalcancer is much more common worldwide, particularly in countries without screening programs, with an estimated 530,000 new cases of the disease and 275,000 resultant deaths each year (3, 4). When cervicalcancer screening programs have been introduced into communities, marked reductions in cervicalcancer incidence have followed (5, 6). New technologies for cervicalcancer screening continue to evolve as do recommendations for managing the results. In addition, there are different risk-benefit considerations for women at different ages, as reflected in age-specific screening recommendations. The ACS, the American Society for Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP) have recently updated their joint guidelines for cervicalcancer screening (7), and an update to the U.S. Preventive Services Task Force recommendations also has been issued (8). The purpose of this document is to provide a review of the best available evidence regarding screening for cervicalcancer. PMID:23090560

Background Multiple studies proved that miRNAs have a causal role in tumorigenesis. Some miRNAs are regulated by epigenetic alterations in their promoter regions and can be activated by chromatin- modifying drugs. Methods We treated cervicalcancercells with 5-aza-2’-deoxycytidine and get a microarray analysis. Dysregulation of miRNAs was measured by qPCR in cervicalcell lines and methylation status of them in cervicalcancer tissue were performed with MeDIP-qPCR assay. Results We found hypermethylation of miR-432, miR-1286, miR-641, miR-1290, miR-1287 and miR-95 may have some relationship with HPV infection in cervicalcell lines. In primary tumors of cervix with paired normal tissue, expression levels of miRNAs were inversely correlated with their DNA methylation status in the cervicalcancercell lines treated with 5-AZA. Conclusions Our results indicate that miRNAs might play a role in the pathogenesis of human cervicalcancer with HPV and identify altered miRNA methylation as a possible epigenetic mechanism involved in their aberrant expression. PMID:23732000

Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is very rare and aggressive. The prognosis is very poor despite multimodal treatment. We report a virgin woman with FIGO stage 4b LCNEC of uterine cervix coexisting with squamous cell carcinoma. An early thirties virgin woman presented with 2-month history of abdominal pain. A chest X-ray showed multiple lung metastatic tumors. A vaginal smear showed malignant cells, and a biopsy specimen had features of LCNEC. The tumor showed trabecular patterns. Tumor cells possessed a moderate amount of cytoplasm, prominent nucleoli, and large nuclei. The tumor cells are stained positive for synaptophysin, chromogranin A, and neuron specific enolase (NSE). The invasive tumor cells in connection with cervical squamous epithelium were focally positive for 34bE12. We made a diagnosis of composite LCNEC and nonkeratinizing squamous cell carcinoma. High-risk HPV test was negative with hybridized captured method 2. PMID:24062959

ABSTRACT Human papillomavirus 45 (HPV45) is a member of the HPV18-related alpha-7 species and accounts for approximately 5% of all cervicalcancer cases worldwide. This study evaluated the genetic diversity of HPV45 and the association of HPV45 variants with the risk of cervicalcancer by sequencing the entire E6 and E7 open reading frames of 300 HPV45-positive cervical samples from 36 countries. A total of 43 HPV45 sequence variants were identified that formed 5 phylogenetic sublineages, A1, A2, A3, B1, and B2, the distribution of which varied by geographical region. Among 192 cases of cervicalcancer and 101 controls, the B2 sublineage was significantly overrepresented in cervicalcancer, both overall and in Africa and Europe separately. We show that the sequence analysis of E6 and E7 allows the classification of HPV45 variants and that the risk of cervicalcancer may differ by HPV45 variant sublineage. IMPORTANCE This work describes the largest study to date of human papillomavirus 45 (HPV45)-positive cervical samples and provides a comprehensive reference for phylogenetic classification for use in epidemiological studies of the carcinogenicity of HPV45 genetic variants, particularly as our findings suggest that the B2 sublineage of HPV45 is associated with a higher risk of cervicalcancer. PMID:24501412

To explore whether hypoxia and interleukin 8 (IL-8) regulate the viability and apoptosis of cervical carcinomas cells and the possible mechanism. We evaluated the expression of hypoxia inducible factor-1? (HIF-1?), IL-8 and its receptors (CXCR1 and CXCR2) in cervicalcancer and cervicitis tissues by immunohistochemistry. Then the effects of hypoxia and IL-8 on the viability and apoptosis of HeLa and SiHa cells were detected by the SRB and apoptosis assays. Here we observed that the expression of HIF-1?, IL-8 and CXCR1 in cervicalcancer tissues was significantly higher than that in cervicitis tissues. Hypoxic condition stimulated the secretion of IL-8 and the expression of CXCR1 and CXCR2 on HeLa and SiHa cells. Recombinant human IL-8 enhanced the viability and reduced the apoptosis in HeLa and SiHa cells. HeLa and SiHa cells cultured in 1% oxygen showed the increased viability and apoptosis, and the former effect could be partly reversed by anti-human IL-8 neutralizing antibody. This data suggested that IL-8 secreted by cervical carcinomas cells induced by hypoxia can stimulate the viability of cervical carcinomas cells in an autocrine dependent manner, and contribute to the pathogenesis of cervicalcancer. PMID:24551277

Abstract Background. As carriers of filaggrin gene (FLG) mutations may have a compromised cervical mucosal barrier against human papillomavirus infection, our primary objective was to study their risk of cervicalcancer. Methods. We genotyped 586 cervicalcancer patients for the two most common FLG mutations, R501X and 2282del4, using blood from the Copenhagen Hospital Biobank, Denmark. Controls (n = 8050) were genotyped in previous population-based studies. Information on cervicalcancer, mortality and emigration were obtained from national registers. Odds ratios (OR) were estimated by logistic regression with adjustment for age at blood sampling, and weighted by the genotype-specific inverse probability of death between diagnosis and sampling. Hazard ratios (HR) were estimated by Cox regression with time since diagnosis as underlying time, and with adjustment for age at diagnosis and stratification by cancer stage. Results. The primary results showed that FLG mutations were not associated with the risk of cervicalcancer (6.3% of cases and 7.7% of controls were carriers; OR adjusted 0.81, 95% CI 0.57-1.14; OR adjusted+ weighted 0.96, 95% CI 0.58-1.57). Among cases, FLG mutations increased mortality due to cervicalcancer (HR 4.55, 95% CI 1.70-12.2), however, the association was reduced after stratification by cancer stage (HR 2.53, 95% CI 0.84-7.59). Conclusion. Carriage of FLG mutations was not associated with the risk of cervicalcancer. PMID:25383447

Several reports have described the potential effects of natural compounds as anti-cancer agents in vitro as well as in vivo. The aim of this study was to evaluate the anti-cancer effect of Limoniastrum guyonianum aqueous gall extract (G extract) and luteolin in the human cervicalcancer HeLa cell line, and, if so, to clarify the underlying mechanism. Our results show that G extract and luteolin inhibited cell proliferation and induced G2/M cell cycle arrest in a concentration and time-dependent manner. Both natural products induced programmed cell death as confirmed by the presence of hypodiploid G0/G1 cells. These effects are associated with an up-regulation of the expression of the tumor suppressor gene p16INK4A and a down-regulation of the expression of the anti-apoptotic actor UHRF1 and its main partner DNMT1. Moreover, G extract- and luteolin-induced UHRF1 and DNMT1 down-regulation is accompanied with a global DNA hypomethylation in HeLa cell line. Altogether our results show that G extract mediates its growth inhibitory effects on human cervicalcancer HeLa cell line likely via the activation of a p16INK4A -dependent cell cycle checkpoint signalling pathway orchestrated by UHRF1 and DNMT1 down-regulation. PMID:23688286

Two-photon activated photodynamic therapy (2-? PDT) has the potential of treating deeper tumors and/or improving tumor targeting. Here, we evaluated the one- and two-photon activated PDT efficacy of pyropheophorbide-a methyl ester (MPPa), a second-generation photosensitizer derived from chlorophyll a. We show that MPPa, when activated by femtosecond (fs) laser pulses at 674 nm, has high one-photon (1-?) PDT efficacy against cisplatin-sensitive human cervical (HeLa) and cisplatin-resistant human lung (A549) and ovarian (NIH:OVCAR-3) cancercells. At a low light dose of 0.06 J cm(-2), the IC50 (the MPPa concentration required to kill 50% of the cells) was determined to be 5.3 ± 0.3, 3.4 ± 0.3 and 3.6 ± 0.4 ?M for HeLa, A549 and NIH:OVCAR-3 cells, respectively. More significantly, we also show that MPPa can be effectively activated by an 800 nm, 120 fs laser through 2-? excitation; at a light dose causing no measurable photocytotoxicity in the absence of photosensitizer, the corresponding IC50 values were measured to be 4.1 ± 0.3, 9.6 ± 1.0 and 1.6 ± 0.3 ?M, respectively. These results indicate that MPPa is a potent photosensitizer for both 1- and 2-? activated PDT with potential applications for difficult-to-treat tumors by conventional therapies. PMID:24607610

Cervicalcancer is the third most common cause of cancer in women in the world. During the past few decades tremendous strides have been made toward decreasing the incidence and mortality of cervicalcancer with the implementation of various prevention and screening strategies. The causative agent linked to cervicalcancer development and its precursors is the human papillomavirus (HPV). Prevention and screening measures for cervicalcancer are paramount because the ability to identify and treat the illness at its premature stage often disrupts the process of neoplasia. Cervical carcinogenesis can be the result of infections from multiple high-risk HPV types that act synergistically. This imposes a level of complexity to identifying and vaccinating against the actual causative agent. Additionally, most HPV infections spontaneously clear. Therefore, screening strategies should optimally weigh the benefits and risks of screening to avoid the discovery and needless treatment of transient HPV infections. This article provides an update of the preventative and screening methods for cervicalcancer, mainly HPV vaccination, screening with Pap smear cytology, and HPV testing. It also provides a discussion of the newest United States 2012 guidelines for cervicalcancer screening, which changed the age to begin and end screening and lengthened the screening intervals. PMID:25302174

PURPOSE: The aim of this study was to evaluate efficacy of gynecologic examination under general anesthesia with cervical biopsies after (chemo) radiation for cervicalcancer to identify patients with residual disease who may benefit from salvage surgery. METHODS AND MATERIALS: In a retrospective cohort study data of all cervicalcancer patients with the International Federation of Gynecology and Obstetrics (FIGO)

,000 in the HPV-screened groups, compared with 36 women per 100,000 in the groups screened by Pap smear. Guglielmo and not on the specific protocol, the authors stated. The Pap smear procedure takes a sample of cells from the cervixScreening for HPV Outperforms Pap Test for CervicalCancer Published on Cancer Network (http

Counseling messages for tobacco cessation, condom use, circumcision, and selective choice in the number of sexual partners can help reduce the risk of cervicalcancer. Other sexual behavioral and reproductive risk factors for cervicalcancer are a younger age at first intercourse and at first full-term pregnancy as well as increasing duration of combined hormonal oral contraceptive use. Micronutrients and supplements can reduce the risk of human papillomavirus infection, persistence, progression, and regression. Some human papillomavirus infections can be prevented by vaccination. Cervicalcancer is best prevented by screening. PMID:24686336

Recently members of mammalian patatin-like phospholipase domain containing (PNPLA) protein family have attracted attention for their critical roles in diverse aspects of lipid metabolism and signal pathway. Until now little has been known about the characteristics of PNPLA1. Here, the full length coding cDNA sequence of human PNPLA1 (hPNPLA1) was cloned for the first time, which encoded a polypeptide with 532 amino acids containing the whole patatin domain. Tissue expression profiles analysis showed that low mRNA levels of hPNPLA1 existed in various tissues, except high expression in the digestive system, bone marrow and spleen. Subcellular distribution of hPNPLA1 tagged with green fluorescence protein mainly localized to lipid droplets. Furthermore, a nonsense mutation of PNPLA1 in human cervicalcancer HeLa cells was identified. The hPNPLA1 mutant encoded a protein of 412 amino acids without the C-terminal domain and did not colocalize to lipid droplets, which suggested that the C-terminal region of hPNPLA1 affected lipid droplet binding. These results identified hPNPLA1 and a mutant in HeLa cells, and provided insights into the structure and function of PNPLA1. PMID:24057234

Background MicroRNA expression is severely disrupted in carcinogenesis, however limited evidence is available validating results from cell-line models in human clinical cancer specimens. MicroRNA-21 (mir-21) and microRNA-143 (mir-143) have previously been identified as significantly deregulated in a range of cancers including cervicalcancer. Our goal was to investigate the expression patterns of several well-studied microRNA species in cervical samples and compare the results to cell line samples. Methodology/Principal Findings We measured the expression of mir-21 and mir-143 in 142 formalin-fixed, paraffin embedded (FFPE) cervical biopsy tissue blocks, collected from Dantec Oncology Clinic, Dakar, Senegal. MicroRNA expression analysis was performed using Taqman-based real-time PCR assays. Protein immunohistochemical staining was also performed to investigate target protein expression on 72 samples. We found that mir-21 expression increased with worsening clinical diagnosis but that mir-143 was not correlated with histology. These observations were in stark contrast to previous reports involving cervicalcancercell lines in which mir-143 was consistently down-regulated but mir-21 largely unaffected. We also identified, for the first time, that cytoplasmic expression of Programmed Cell Death Protein 4 PDCD4; a known target of mir-21) was significantly lower in women with invasive cervical carcinoma (ICC) in comparison to those with cervical intraepithelial neoplasia (2–3) or carcinoma in situ (CIN2-3/CIS), although there was no significant correlation between mir-21 and PDCD4 expression, despite previous studies identifying PDCD4 transcript as a known mir-21 target. Conclusions Whilst microRNA biomarkers have a number of promising features, more studies on expression levels in histologically defined clinical specimens are required to investigate clinical relevance of discovery-based studies. Mir-21 may be of some utility in predictive screening, given that we observed a significant correlation between mir-21 expression level and worsening histological diagnosis of cervicalcancer. PMID:22194833

Despite cervicalcancer being potentially preventable, it is the second most common cancer among women in Malaysia. One hundred and five articles related to CervicalCancer were found in a search through a database dedicated to indexing all original data relevant to medicine published in Malaysia between the years 2000-2013. Fifty seven articles were selected and reviewed for the articles' clinical relevance and future research implications. This article reviews the various aspects of cervicalcancer in Malaysia, mainly persistent infection of high risk human papillomavirus (HPV), primary prevention (HPV vaccination), screening method (Pap smear issues), and the attitude and knowledge of various groups of Malaysian women that contributed to the failure to reduce the incidence and mortality of cervicalcancer. Most of the studies focused on prevention, Pap smear issues, HPV DNA testing, HPV vaccination and various recommendations for prevention of cervicalcancer. Secondary prevention by screening is still an important aspect because even with HPV vaccination, screening still plays an important role as vaccination does not cover all high risk HPVs. There is a need to seriously consider a properly organised screening programme, taking into consideration what we already know about the attitude and knowledge of Malaysian women, economic factors and psychosocial issues of the screening method. There is also a large gap in clinical studies on the outcome, management and survival of cervicalcancer patients in Malaysia. PMID:25417949

In the current study, the fluorescence emission spectra (FES) and Stokes shift spectra (SSS) of blood and urine samples of cervicalcancer patients were obtained and compared to those of normal controls. Both spectra showed that the relative intensity of biomolecules such as porphyrin, collagen, Nicotinamide adenine dinucleotide, and flavin were quite out of proportion in cervicalcancer patients. The biochemical mechanism for the elevation of these fluorophores is not yet definitive; nevertheless, these biomolecules could serve as tumor markers for diagnosis, screening, and follow-up of cervicalcancers. To the best of our knowledge, this is the first report on FES and SSS of blood and urine of cervicalcancer patients to give a sensitivity of 80% and specificity of 78%.

A hallmark of cervicalcancer is the pronounced genetic heterogeneity found within the cells that make up a tumor, particularly in terms of gaining multiple copies of certain genes and losing copies of others.

The use of Raman spectroscopy to analyze the biochemical composition of serum samples and hence distinguish between normal and cervicalcancer serum samples was investigated. The serum samples were obtained from 19 patients who were clinically diagnosed with cervicalcancer, 3 precancer, and 20 healthy volunteer controls. The imprint was put under an Olympus microscope, and around points were chosen for Raman measurement.All spectra were collected at a Horiba Jobin-Yvon LabRAM HR800 Raman Spectrometer with a laser of 830-nm wavelength and 17-mW power irradiation. Raw spectra were processed by carrying out baseline correction, smoothing, and normalization to remove noise, florescence, and shot noise and then analyzed using principal component analysis (PCA). The control serum spectrum showed the presence of higher amounts of carotenoids indicated by peaks at 1,002, 1,160, and 1,523 cm(-1)and intense peaks associated with protein components at 754, 853, 938, 1,002, 1,300-1,345, 1,447, 1,523, 1,550, 1,620, and 1,654 cm(-1). The Raman bands assigned to glutathione (446, 828, and 1,404 cm(-1)) and tryptophan (509, 1,208, 1,556, 1,603, and 1,620 cm(-1)) in cervicalcancer were higher than those of control samples, suggesting that their presence may also play a role in cervicalcancer. Furthermore, weak bands in the control samples attributed to tryptophan (545, 760, and 1,174 cm(-1)) and amide III (1,234-1,290 cm(-1)) seem to disappear and decrease in the cervicalcancer samples, respectively. It is shown that the serum samples from patients with cervicalcancer and from the control group can be discriminated with high sensitivity and specificity when the multivariate statistical methods of PCA is applied to Raman spectra. PCA allowed us to define the wavelength differences between the spectral bands of the control and cervicalcancer groups by confirming that the main molecular differences among the control and cervicalcancer samples were glutathione, tryptophan, ? carotene, and amide III. The preliminary results suggest that Raman spectroscopy could be a highly effective technique with a strong potential of support for current techniques as Papanicolaou smear by reducing the number of these tests; nevertheless, with the construction of a data library integrated with a large number of cervicalcancer and control Raman spectra obtained from a wide range of healthy and cervicalcancer population, Raman-PCA technique could be converted into a new technique for noninvasive real-time diagnosis of cervicalcancer from serum samples. PMID:24197519

Cervicalcancer is one of the most common and lethal gynecological malignancies in both developing and developed countries,\\u000a and therefore, there is a considerable interest in early diagnosis and treatment of precancerous lesions. Although the current\\u000a standard care mainly based on cytology and colposcopy has reduced rates of cervicalcancer morbidity and mortality, many lesions\\u000a are still missed or overcalled

Vascular endothelial growth factor (VEGF) is an important regulator of neovascularization. Hypoxia inducible nitric oxide (NO) enhanced the expression of VEGF and thymosin beta-4 (T?4), actin sequestering protein. Here, we investigated whether NO-mediated VEGF expression could be regulated by T?4 expression in HeLa cervicalcancercells. Hypoxia inducible NO production and VEGF expression were reduced by small interference (si) RNA of T?4. Hypoxia response element (HRE)-luciferase activity and VEGF expression were increased by the treatment with N-(?-D-Glucopyranosyl)-N2-acetyl-S-nitroso-D, L-penicillaminamide (SNAP-1), to generate NO, which was inhibited by the inhibition of T?4 expression with T?4-siRNA. In hypoxic condition, HRE-luciferase activity and VEGF expression were inhibited by the treatment with NG-monomethyl-L-arginine (L-NMMA), an inhibitor to nitric oxide synthase (NOS), which is accompanied with a decrease in T?4 expression. VEGF expression inhibited by L-NMMA treatment was restored by the transfection with pCMV-T?4 plasmids for T?4 overexpression. Taken together, these results suggest that T?4 could be a regulator for the expression of VEGF via the maintenance of NOS activity. PMID:25593639

Structured Abstract Introduction The most common types of cervicalcancer are squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma, referred to here collectively as SA cervicalcancer. Other types of cervicalcancer, referred to here collectively as nonsquamous/nonadenocarcinoma (NSNA) cervicalcancer, include neuroendocrine, small cell, clear cell, sarcomatoid, and serous tumors. Anecdotally, NSNA tumors seem to have a worse prognosis than their SA counterparts. We sought to determine whether patients with early-stage NSNA have a worse prognosis than those with early-stage SA cervicalcancer. Methods We retrospectively reviewed charts of women with stage IA1-IB2 NSNA cervicalcancer treated by radical hysterectomy and lymph node staging at MD Anderson Cancer Center from 1990 to 2006. NSNA patients were matched 1:2 to patients with grade 3 SA lesions on the basis of stage, age at diagnosis, tumor size, and date of diagnosis. Results Eighteen patients with NSNA primary cervicalcancer subtypes [neuroendocrine (n=7), small cell (5), clear cell (4), papillary serous (1), and sarcomatoid (1)] were matched to 36 patients with grade 3 SA lesions. There were no differences between the 2 groups in age, body mass index, clinical stage, or lesion size. The 2 groups also did not differ with respect to number of nodes resected, lymphovascular space invasion, margin status, lymph node metastasis, or adjuvant radiation therapy or chemotherapy. At a median follow-up of 44 months, median progression-free and overall survivals had not been reached; however, both progression-free survival (p=0.018) and overall survival (p=0.028) were worse for the NSNA group. The 5-year progression-free and overall survival rates were 61.2% and 67.6%, respectively, for the NSNA group, compared to 90.1% and 88.3%, respectively, for the SA group. Conclusions Patients with early-stage NSNA cervicalcancer undergoing radical hysterectomy and pelvic lymphadenectomy have a worse prognosis than patients with grade 3 SA lesions. Patients with NSNA tumors may require a multimodality approach to their cancer care. PMID:21178574

It is estimated that Haiti has the highest incidence of cervicalcancer in the Western Hemisphere. There are currently no sustainable and affordable cervicalcancer screening programs in Haiti. The current status of screening services and knowledge of health care professionals was assessed through a Knowledge, Attitudes, and Practices survey on cervicalcancer screening and prevention. It was distributed to Project Medishare for Haiti health care workers (n = 27) in the Central Plateau. The majority (22/27) of participants stated pre-cancerouscells could be detected through screening, however, only four had ever performed a pap smear. All of the participants felt a screening program should be started in their area. Our data establishes that knowledge is fairly lacking among healthcare workers and there is an opportunity to train them in simple, cost effective "screen-and-treat" programs that could have a great impact on the overall health of the population. PMID:25390794

Background- Specific types of high risk Human papillomaviruses (HR-HPVs) particularly, HPV types 16 and 18 cause cervicalcancer and while\\u000a the two recently developed vaccines against these HPV types are prophylactic in nature, therapeutic options for treatment\\u000a and management of already existing HPV infection are not available as yet. Because transcription factor, Activator Protein-1\\u000a (AP-1) plays a central role in HPV-mediated

Background Cervicalcancer is the most common cancer affecting women in Uganda; yet community understanding of the disease is limited. We explored community perceptions, beliefs and knowledge about the local names, causes, symptoms, course, treatment, and prognosis of cervicalcancer in order to inform targeted interventions to promote early help-seeking. Methods Twenty four focus group discussions (FGD) with men and women aged 18 – 59 years and ten key informant interviews with persons aged???60 years were conducted at two sites in Gulu district between May and June 2012. A semi-structured interview guide informed by Kleinman’s illness explanatory model and literature on community awareness of cervicalcancer was used to collect data. Data analysis was supported with use of ATLAS.ti 6.1 in coding, organizing and tracking data segments. We used content analysis technique in data analysis and organised data into a structured format under distinct themes and categories. Results Cervicalcancer was known by the local name “two remo”, meaning “an illness that manifests with bleeding.” Respondents believed that early onset of sexual activity, multiple male sexual partners and multi-parity cause cervicalcancer. Respondents in half of FGDs also reported that use of condoms and family planning pills and injections cause cervicalcancer. Symptoms of cervicalcancer reported included vaginal bleeding, watery vaginal discharge and lower abdominal and waist pain. Respondents in most of the FGDs and key informants perceived cervicalcancer as a chronic illness and that it can be treated with both modern and traditional medicines. The majority thought that cervicalcancer treatment was supportive; the illness is not curable. Conclusions While some lay beliefs about the causes of cervicalcancer suggest some understanding of aetiology of the disease, other perceived causes particularly those related to use of family planning and condoms are potentially hurtful to public health. Awareness campaigns to promote early help-seeking for cervicalcancer symptoms need to be culturally-sensitive and context-specific; and include messages on symptoms, risk factors, course, treatment and prognoses. PMID:25028122

Cervicalcancer remains unique among solid tumor malignancies. Persistent infection with oncogenic subtypes of the human papillomavirus (HPV) results in carcinogenesis, predominantly occurring at the cervical transformation zone where endocervical columnar cells undergo metaplasia to a stratified squamous epithelium. The molecular cascade involving viral oncoproteins, E6 and E7 and their degradative interactions with cellular tumor suppressor gene products, p53 and pRb, respectively, has been precisely delineated. The precursor state of cervical neoplasia may last for years allowing for ready detection through successful screening programs in developed countries using cervical cytology and/or high-risk HPV DNA testing. Prophylactic HPV L1 capsid protein vaccines using virus-like-particle technology have been developed to prevent primary infection by the most common high-risk HPVs (16 and 18). Women who lack access to health care and those who undergo sporadic screening remain at risk. Although radical surgery (including fertility-sparing surgery) is available for patients with early-stage cancers, and chemoradiation plus high-dose-rate brachytherapy can cure the majority of those with locally advanced disease, patients with metastatic and nonoperable recurrent cervicalcancer constitute a high-risk population with an unmet clinical need. On August 14, 2014, the FDA approved the antiangiogenesis drug bevacizumab for women with advanced cervicalcancer. This review will highlight advances in translational science, antiangiogenesis therapy and immunotherapy for advanced disease. PMID:25104084

Protein profiles of homogenized normal cervical tissue samples from hysterectomy subjects and cancerouscervical tissues from biopsy samples collected from patients with different stages of cervicalcancer were recorded using High Performance Liquid Chromatography coupled with Laser Induced Fluorescence (HPLC-LIF). The Protein profiles were subjected to Principle Component Analysis to derive statistically significant parameters. Diagnosis of sample types were carried out by matching three parameters—scores of factors, squared residuals, and Mahalanobis Distance. ROC and Youden's Index curves for calibration standards were used for objective estimation of the optimum threshold for decision making and performance.

Contributions in the domain of cancer research: Review Human papillomaviruses and their role papillomaviruses (HPVs) have been linked to a variety of human diseases, most notably can- cer of the cervix of cervicalcancer. Key words. Cervicalcancer; papillomavirus; gene expression; viral oncogene; early protein

Although cervicalcancer is one of the most commonly diagnosed cancers among Vietnamese American women (VAW) and Korean American women (KAW), both groups consistently report much lower rates of cervicalcancer screening compared with other Asian ethnic subgroups and non-Hispanic Whites. This study aimed to explore multilevel factors that may underlie low screening rates among VAW and KAW living in a city where their ethnic communities are relatively small. The socioecological model was used as a conceptual framework. Thirty participants were conveniently recruited from ethnic beauty salons run by VA and KA cosmetologists in Albuquerque, New Mexico. The participants' average age was 44.6 years (SD = .50; range = 21-60). Most participants were married (80 %) and employed (73.3 %), and had health insurance (83.3 %). A qualitative interview was conducted in Vietnamese or Korean and transcribed verbatim. A thematic content analysis was used to identify major codes, categories, and patterns across the transcripts. The study identified several factors at the individual (e.g., pregnancy, poverty, personality), interpersonal (e.g., family responsibility, mother as influential referent), and community (e.g., lack of availability, community size) levels. The study sheds light on four major areas that must be taken into consideration in the development of culturally appropriate, community-based interventions aimed to reduce disparities in cervicalcancer screening among ethnic minority women in the United States: (1) ethnic community size and geographic location; (2) cross-cultural similarities and dissimilarities; (3) targeting of not only unmarried young women, but also close referents; and (4) utilization of trusted resources within social networks. PMID:24863746

Despite the high prevalence of both human papillomavirus (HPV) infections and cervicalcancer among Zimbabwean women, the ability to test for HPV infection of the uterine cervix is limited by a lack of an easy sample collection method that does not require gynecological examination. The presence of HPVs in urine and cervical swab samples collected from 43 women who presented with invasive cervicalcancer was investigated. HPV detection was done by means of degenerate primers in a nested polymerase chain reaction (PCR). Typing of HPVs was done using restriction fragment length polymorphism (RFLP) analysis. HPV was identified and typed in 98% (42/43) of cervical swabs and 72% (31/43) of paired urine samples. HPV type 16 was the most common (25/42, 59%), followed by types: 33 (13/42, 31%), 18 (6/42, 14%), and 31 (1/42, 2%). Type-specific concordance between cervical and urine samples was high (22/28, 79%). Therefore, the HPV types identified in urine samples in most cases represent the same HPV type infecting the cervical epithelium. The results suggest that urine may be a practical sample for testing of HPV urogenital infection. Further research is required before the detection of HPV in urine can be applied in the routine cervical screening programs. PMID:12858416

Musashi RNA-binding protein1 (Msi1), a member of the RNA-binding protein family, has been reported to be a diagnostic marker and potential therapeutic target in some cancers, its function in cervicalcancer remains unknown. In this study, we found Msi1 was highly expressed in cervicalcancer tissues, and over-expressing Msi1 in cervicalcancercells enhanced tumor formation and cell proliferation and accelerated cells into the S phase. Whereas, down-regulating Msi1 by shRNA in cervicalcancercells inhibited tumor formation and cell proliferation and slowed cell into the S phase, suggesting that Msi1 might act as cell cycle regulator. Immunohistochemistry assay showed the negative correlation between Msi1 and p21, p27 and p53, suggesting that Msi1 might regulate these cycle regulators in cervicalcancer. Moreover, the expression of the p21, p27 and p53 proteins were down-regulated in Msi1 overexpressing cervicalcancercells and up-regulated in shMsi1 cervicalcancercells. Luciferase assays and RNA-protein binding assays confirmed that Msi1 could bind to the mRNA 3?UTRs of p21, p27 and p53 and suppress the translation of these proteins. Our findings provide new evidence that Msi1 might promote cell proliferation by accelerating the cell cycle by directly targeting p21, p27 and p53. PMID:25362645

While persistent infection with oncogenic types of human Papillomavirus (HPV) is required for cervical epithelial cell transformation and cervical carcinogenesis, HPV infection alone is not sufficient to induce tumorigenesis. Only a minor fraction of HPV infections produce high-grade lesions and cervicalcancer, suggesting complex host-virus interactions. Based on its pronounced immunoinhibitory properties, human leukocyte antigen (HLA)-G has been proposed as a possible prognostic biomarker and therapeutic target relevant in a wide variety of cancers and viral infections, but to date remains underexplored in cervicalcancer. Given the possible influence of HLA-G on the clinical course of HPV infection, cervical lesions and cancer progression, a better understanding of HLA-G involvement in cervical carcinogenesis might contribute to two aspects of fundamental importance: 1. Characterization of a novel diagnostic/prognostic biomarker to identify cervicalcancer and to monitor disease stage, critical for patient screening; 2. Identification of HLA-G-driven immune mechanisms involved in lesion development and cancer progression, leading to the development of strategies for modulating HLA-G expression for treatment purposes. Thus, this systematic review explores the potential involvement of HLA-G protein expression and polymorphisms in cervical carcinogenesis. PMID:25453366

Background Cervicalcancer remains the leading cause of cancer death among women in sub-Saharan Africa. In Malawi, very few women have undergone screening and the incidence of cervicalcancer is on the increase as is the case in most developing countries. We aimed at exploring and documenting health system gaps responsible for the poor performance of the cervicalcancer prevention program in Malawi. Design The study was carried out in 14 randomly selected districts of the 29 districts of Malawi. All cervicalcancer service providers in these districts were invited to participate. Two semi-structured questionnaires were used, one for the district cervicalcancer coordinators and the other for the service providers. The themes of both questionnaires were based on World Health Organization (WHO) health system frameworks. A checklist was also developed to audit medical supplies and equipment in the cervicalcancer screening facilities. The two questionnaires together with the medical supplies and equipment checklist were piloted in Chikwawa district before being used as data collection tools in the study. Quantitative data were analyzed using STATA and qualitative in NVIVO. Results Forty-one service providers from 21 health facilities and 9 district coordinators participated in the study. Our findings show numerous health system challenges mainly in areas of health workforce and essential medical products and technologies. Seven out of the 21 health facilities provided both screening and treatment. Results showed challenges in the management of the cervicalcancer program at district level; inadequate service providers who are poorly supervised; lack of basic equipment and stock-outs of basic medical supplies in some health facilities; and inadequate funding of the program. In most of the health facilities, services providers were not aware of the policy which govern their work and that they did not have standards and guidelines for cervicalcancer screening and treatment. Conclusion Numerous health system challenges are prevailing in the cervicalcancer prevention program in Malawi. These challenges need to be addressed if the health system is to improve on the coverage of cervicalcancer screening and treatment. PMID:25623612

Carcinoembryonic antigen (CEA) and squamous cell carcinoma(SCC) serum levels were prospectively determined in 159 untreated patients diagnosed with carcinoma of the uterine cervix from 1991 to 2001. The histological analysis showed epidermoid cancer in 117 patients, adenocarcinoma in 26 patients, adenosquamous carcinoma in 12 patients and other histological types in the remaining 4 patients. Tumor marker sensitivity was related to the histological type with abnormal SCC (>2 ng/ml) in 51.3% of squamous tumors in contrast to the 7.1% found in other histologies. By contrast, CEA sensitivity was not related to histology with abnormal values (>5 ng/ml) in 25% of squamous tumors, 19% of adenocarcinomas, 33% of adenosquamous carcinomas and 25% of other histologies. CEA and SCC serum levels were clearly related to tumor stage, parametrial invasion, tumor size and nodal involvement. Elevated pretreatment CEA indicates parametrial invasion with a probability of 82%. Likewise, pretreatment CEA and SCC serum levels were of prognostic value, with a shorter disease-free survival and overall survival in patients with abnormal levels. All patients with adenocarcinomas and abnormal CEA had relapse during follow-up. Multivariate analysis indicated that parametrial invasion, age, tumor size and SCC were independent prognostic factors. In conclusion, CEA and SCC are useful tumor markers in carcinomas of the uterine cervix, with a clear relationship with well-known prognostic factors (parametrial invasion, nodal involvement), and are of prognostic value. PMID:14610320

OBJECTIVE To analyze cervical and breast cancer mortality in Brazil according to socioeconomic and welfare indicators. METHODS Data on breast and cervicalcancer mortality covering a 30-year period (1980-2010) were analyzed. The data were obtained from the National Mortality Database, population data from the Brazilian Institute of Geography and Statistics database, and socioeconomic and welfare information from the Institute of Applied Economic Research. Moving averages were calculated, disaggregated by capital city and municipality. The annual percent change in mortality rates was estimated by segmented linear regression using the joinpoint method. Pearson’s correlation coefficients were conducted between average mortality rate at the end of the three-year period and selected indicators in the state capital and each Brazilian state. RESULTS There was a decline in cervicalcancer mortality rates throughout the period studied, except in municipalities outside of the capitals in the North and Northeast. There was a decrease in breast cancer mortality in the capitals from the end of the 1990s onwards. Favorable socioeconomic indicators were inversely correlated with cervicalcancer mortality. A strong direct correlation was found with favorable indicators and an inverse correlation with fertility rate and breast cancer mortality in inner cities. CONCLUSIONS There is an ongoing dynamic process of increased risk of cervical and breast cancer and attenuation of mortality because of increased, albeit unequal, access to and provision of screening, diagnosis and treatment. PMID:25119941

At least 12,000 women are diagnosed with cervicalcancer each year in the United States, accounting for at least 4,000 deaths. Worldwide, cervicalcancer is the second most common type of cancer among women. The human papilloma virus (HPV) has been linked to at least 70% of all cervicalcancer. HPV can be divided into 2 categories: (a) low risk,…

Purpose We analyzed patterns and factors associated with receipt of breast and cervicalcancer screening in a cohort of colorectal cancer survivors. Methods Individuals diagnosed with colorectal cancer in Nova Scotia between January 2001 and December 2005 were eligible for inclusion. Receipt of breast and cervicalcancer screening was determined using administrative data. General-population age restrictions were used in the analysis (breast: 40–69 years; cervical: 21–75 years). Kaplan–Meier and Cox proportional hazards models were used to assess time to first screen. Results Of 318 and 443 colorectal cancer survivors eligible for the breast and cervicalcancer screening analysis respectively, 30.1% [95% confidence interval (ci): 21.2% to 39.0%] never received screening mammography, and 47.9% (95% ci: 37.8% to 58.0%) never received cervicalcancer screening during the study period. Receipt of screening before the colorectal cancer diagnosis was strongly associated with receipt of screening after diagnosis (hazard ratio for breast cancer screening: 4.71; 95% ci: 3.42 to 6.51; hazard ratio for cervicalcancer screening: 6.83; 95% ci: 4.58 to 10.16). Conclusions Many colorectal cancer survivors within general-population screening age recommendations did not receive breast and cervicalcancer screening. Future research should focus on survivors who meet age recommendations for population-based cancer screening. PMID:25302037

The management of recurrent cervicalcancer depends mainly on previous treatment and on the site and extent of recurrence. Concurrent cisplatin-based chemo-radiation is the treatment of choice for patients with pelvic failure after radical hysterectomy alone. However, the safe delivery of high doses of radiotherapy is much more difficult in this clinical setting compared with primary radiotherapy. Pelvic exenteration usually represents the only therapeutic approach with curative intent for women with central pelvic relapse who have previously received irradiation. In a recent series, the 5-year overall survival and operative mortality after pelvic exenteration ranged from 21 to 61% and from 1 to 10%, respectively. Free surgical margins, negative lymph nodes, small tumour size and long disease-free interval were associated with a more favourable prognosis. Currently, pelvic reconstructive procedures (continent urinary conduit, low colorectal anastomosis, vaginal reconstruction with myocutaneous flaps) are strongly recommended after exenteration. Concurrent cisplatin-based chemo-radiation is the treatment of choice for isolated para-aortic lymph node failure, with satisfactory chances of a cure in asymptomatic patients. Chemotherapy is administered with palliative intent to women with distant or loco-regional recurrences not amenable by surgery or radiotherapy. Cisplatin is the most widely used drug, with a response rate of 17–38% and a median overall survival of 6.1–7.1 months. Cisplatin-based combination chemotherapy achieves higher response rates (22–68%) when compared with single-agent cisplatin, but median overall survival is usually less than one year. In a recent Gynecologic Oncology Group (GOG) trial the combination topotecan + cisplatin obtained a significantly longer overall survival than single-agent cisplatin in patients with metastatic or recurrent or persistent cervicalcancer. A subsequent GOG study showed a trend in terms of longer overall survival and better quality of life for the doublet cisplatin + paclitaxel vs. the doublets cisplatin + topotecan, cisplatin + vinorelbine, and cisplatin + gemcitabine. Molecularly targeted therapy may represent a novel therapeutic tool, but its use alone or in combination with chemotherapy is still investigational. PMID:22966247

URI, or RMP, is a RNA polymerase II subunit RPB5-associated protein known to play essential roles in ubiquitination and transcription. Recently, we and others have shown that URI/RMP is also important for progression of hepatocellular carcinoma, ovarian, and prostate cancers. To identify the mechanistic basis of URI/RMP during multiple cellular processes, we investigated URI/RMP expression in a tissue microarray (TMA) containing multiple normal human tissues. The results showed that URI/RMP is ubiquitously but differentially expressed in these human tissues which partially explains its multiple cellular functions. To elucidate the role of URI/RMP during oncogenesis of multiple malignancies, especially the tumors of reproductive system, we analyzed URI/RMP expression in a TMA containing multiple reproductive system tumors. We did not observe significant difference of URI/RMP expression between cancerous and adjacent tissues of the prostate, breast, ovarian, and endometrial cancers. However, increased URI/RMP expression was observed in two of the three cases of cervical SCC (squamous cell carcinoma) cells compared to their adjacent epithelial cells. Moreover, we detected significantly upregulated URI/RMP expression not only in cervicalcancers but also in pre-cancerous CINs (cervical intra-epithelial neoplasias) in a TMA that covers the whole spectrum of normal cervix, CINs, and cervicalcancers. No difference of URI/RMP expression was observed between CINs and cervicalcancers. Given the high risk of CINs (especially CIN3) turning into cervicalcancer if left untreated, the increased URI/RMP expression in CINs as well as in cervicalcancers suggest a clinical relevance of URI/RMP upon cervicalcancer tumorigenesis and worth further investigation. PMID:23573313

Identification of high-risk HPV genotypes in patients is essential for vaccination and prevention programs while the geographic distribution of cervicalcancer varies widely. HPV 16 is the major cause of cervicalcancer followed by HPV 18, HPV 31, HPV 52, or HPV 58 depending on geographic area. In this study, the distribution of HPV genotypes in cervical specimens from women living in Thailand was analyzed by HPV testing with electrochemical DNA chip and PCR direct sequencing. The 716 specimens were grouped according to their cytological grades; 100 normal, 100 low-grade squamous intraepithelial lesions, 100 high grade squamous intraepithelial lesions, and 416 specimens of cervicalcancer. The results showed that HPV 16, HPV 18, HPV 52, and HPV 58 are the most common HPV genotypes in Thailand, respectively. With respect to age, women below the age of 26 years were almost negative for high-risk HPV DNA exclusively. Conversely, high prevalence of high-risk HPV DNA and abnormal cytology were usually found in women between 26 and 45 years while cervicalcancer was detected mainly in women above the age of 45 years. To increase protection efficiency, a vaccine including HPV 52 and HPV 58 should be offered to Asian women, and primary HPV screening should start at 26-30 years of age. PMID:24127280

Acquired chemo-resistance is one of the key causal factors in cancer death. Emerging evidences suggest that miRNA and epithelial–mesenchymal transition play critical roles in the chemo-resistance in cancers. Here, we showed the association of paclitaxel-resistance with miR-375 over-expression and epithelial–mesenchymal transition inducement in cervicalcancer. Using different cervicalcancercell models, we found that paclitaxel transiently induced up-regulation of miR-375 expression, proliferation inhibition, transition from epithelial to mesenchymal phenotype, and consequently impaired paclitaxel sensitivity. Forced over-expression of miR-375 may suppress Ecadherin expression by a directly targeting pathway, which led to paclitaxel resistance. Contrarily, re-expression of Ecadherin partly reversed epithelial–mesenchymal transition phenotype and miR-375 induced paclitaxel-resistance. Our findings suggest that paclitaxel-induced miR-375 over-expression facilitates epithelial–mesenchymal transition process via directly targeting Ecadherin, proliferation inhibition, and consequently results in chemo-resistance in cervicalcancercells. A reversion of miR-375 or Ecadherin expression may be a novel therapeutic approach for overcoming chemo-resistance in cervicalcancer. PMID:25330011

Human cervical carcinoma cell lines that were either positive or negative for human papillomavirus (HPV) DNA sequences were analyzed for evidence of mutation of the p53 and retinoblastoma genes. Each of five HPV-positive cervicalcancercell lines expressed normal pRB and low levels of wild-type p53 proteins, which are presumed to be altered in function as a consequence of association

Accurate classification of Pap smear images becomes the challenging task in medical image processing. This can be improved in two ways. One way is by selecting suitable well defined specific features and the other is by selecting the best classifier. This paper presents a nominated texture based cervicalcancer (NTCC) classification system which classifies the Pap smear images into any one of the seven classes. This can be achieved by extracting well defined texture features and selecting best classifier. Seven sets of texture features (24 features) are extracted which include relative size of nucleus and cytoplasm, dynamic range and first four moments of intensities of nucleus and cytoplasm, relative displacement of nucleus within the cytoplasm, gray level cooccurrence matrix, local binary pattern histogram, tamura features, and edge orientation histogram. Few types of support vector machine (SVM) and neural network (NN) classifiers are used for the classification. The performance of the NTCC algorithm is tested and compared to other algorithms on public image database of Herlev University Hospital, Denmark, with 917 Pap smear images. The output of SVM is found to be best for the most of the classes and better results for the remaining classes. PMID:25649913

High attendance is essential to cervicalcancer screening results. Attendance in the Finnish program is currently at 70%, but extensive opportunistic screening occurs beside the organized. A shift from opportunistic to organized screening is imperative to optimize the costs and impact of screening and minimize potential harms. We evaluated the effect of reminder letters (1st reminder) and self-sampling test (2nd reminder) on program attendance. The study population consisted of 31,053 screening invitees in 31 Finnish municipalities. 8,284 non-attendees after one invitation received a reminder letter and 4,536 further non-attendees were offered a self-sampling option. Socioeconomic factors related to participation were clarified by combining screening data to data from Statistics Finland. Reminder letters increased participation from 72.6% (95% CI 72.1, 73.1) to 79.2% (95% CI 78.8, 79.7) and self-sampling further to 82.2% (95% CI 81.8, 82.7). Reminder letters with scheduled appointments resulted in higher increase than open invitations (10 vs. 6%). Screening of original non-attendees increased the yield of CIN3+ lesions by 24%. Non-attendance was associated with young age, immigrant background, lower education level and having never been married. We showed that a total attendance of well over 80% can be achieved within an organized program when the invitational protocol is carefully arranged. PMID:25178683

Cancer is one of the contagious diseases that become a public health issue, both in the world and in Indonesia. In the world, 12% of all deaths caused by cancer and is the second killer after cardiovascular disease. Early detection using the IVA is a practical and inexpensive (only requiring acetic acid). However, the accuracy of the method is quite low, as it can not detect the stage of the cancer. While other methods have a better sensitivity than the IVA method, is a method of PAP smear. However, this method is relatively expensive, and requires an experienced pathologist-cytologist. According to the case above, Considered important to make the cancercervics detector that is used to detect the abnormality and cervicalcancer stage and consists of a digital microscope, as well as a computer application based on artificial neural network. The use of cervicalcancer detector software and hardware are integrated each other. After the specifications met, the steps to design the cervicalcancer detection are: Modifying a conventional microscope by adding a lens, image recording, and the lights, Programming the tools, designing computer applications, Programming features abnormality detection and staging of cancer.

Purpose: Studies have shown that women who engage in high levels of physical activity have higher rates of cancer screening, including Papanicalaou (Pap) tests. Because American Indian (AI) women are at high risk for cervicalcancer morbidity and mortality, we examined Pap screening prevalence and assessed whether physical activity was associated…

OBJECTIVE: This study aimed to evaluate the impact of cancer treatment on bone mineral density (BMD) in the lumbar spine (LS) and femur in the postmenopausal women with cervical or endometrial cancer without bone metastasis compared to normal control postmenopausal women. METHODS: We retrospectively evaluated the BMD data in the LS, femur neck (FN) and trochanter (FT) by dual-energy X-ray absorptiometry and laboratory data of bone turnover markers at baseline and after one year in 130 patients with cervicalcancer, 68 patients with endometrial cancer, and 225 healthy controls. RESULTS: There were no significant differences in the T-scores of basal BMD in LS and femur between patients with endometrial cancer and controls, and only T-score of basal BMD at the fourth lumbar vertebra (L4) was significantly lower in patients with cervicalcancer compared to controls. One year later, T-scores of BMD at all LS sites and FN in patients with cervicalcancer and T-scores of BMD at L3, L4, FN, and FT in those with endometrial cancer after cancer treatment were significantly lower compared to controls. Lower proportions of normal BMD at all skeletal sites except L2 in patients with endometrial cancer and those at L1, L4, and FN in patients with cervicalcancer were observed compared to controls after cancer treatment. CONCLUSIONS: Our results suggest that cancer treatment increase bone loss in postmenopausal women with cervical and endometrial cancer. PMID:25553092

In this study, we have investigated the role of endoglin (CD105), a regulator of transforming growth factor (TGF)-?1 signalling on endothelial cells, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor-A (VEGF-A) in cervicalcancer. We have measured the number and determined the location of both newly formed (CD105-positive) and the overall number of (CD31-positive) blood vessels, and bFGF and VEGF-A expression using immunohistochemistry in 30 cervical carcinoma specimens. Vascular endothelial growth factor-A mRNA expression was determined using RNA-in situ hybridisation. CD105- and CD31-positive vessels and bFGF- and VEGF-A-positive cells were predominantly present in the stroma. The presence of CD105- and CD31-positive vessels in the stroma did neither correlate with the number of VEGF-A-positive cells nor the number of bFGF-positive cells. However, the number of CD105- and CD31-positive vessels was associated with the expression of VEGF-A mRNA in the epithelial cell clusters (P=0.013 and P=0.005, respectively). The presence of CD105-positive and CD31-positive vessels was associated with the expression of ?v?6 (a TGF-?1 activator; P=0.013 and P=0.006, respectively). Clinically, the number of CD105-positive vessels associated with the number of lymph node metastasis (P<0.001). Furthermore, the presence of CD105-positive vessels within the epithelial cell clusters associated with poor disease-free survival (P=0.007). PMID:19352388

In this study, we have investigated the role of endoglin (CD105), a regulator of transforming growth factor (TGF)-beta(1) signalling on endothelial cells, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor-A (VEGF-A) in cervicalcancer. We have measured the number and determined the location of both newly formed (CD105-positive) and the overall number of (CD31-positive) blood vessels, and bFGF and VEGF-A expression using immunohistochemistry in 30 cervical carcinoma specimens. Vascular endothelial growth factor-A mRNA expression was determined using RNA-in situ hybridisation. CD105- and CD31-positive vessels and bFGF- and VEGF-A-positive cells were predominantly present in the stroma. The presence of CD105- and CD31-positive vessels in the stroma did neither correlate with the number of VEGF-A-positive cells nor the number of bFGF-positive cells. However, the number of CD105- and CD31-positive vessels was associated with the expression of VEGF-A mRNA in the epithelial cell clusters (P=0.013 and P=0.005, respectively). The presence of CD105-positive and CD31-positive vessels was associated with the expression of alphavbeta6 (a TGF-beta(1) activator; P=0.013 and P=0.006, respectively). Clinically, the number of CD105-positive vessels associated with the number of lymph node metastasis (P<0.001). Furthermore, the presence of CD105-positive vessels within the epithelial cell clusters associated with poor disease-free survival (P=0.007). PMID:19352388

Ovarian cancer is the fifth most common cancer (neoplasm) among women and the third most common gynecological cancer behind endometrial and cervicalcancer (1). Epithelial ovarian cancer (EOC) represents ~90% of all ovarian cancers. Recently, we have observed the novel expression of the nuclear receptor, the germ cell nuclear factor (GCNF) in several ovarian cancercell lines. This is noteworthy

Human papilloma virus (HPV) is the well-established etiological factor of cervicalcancer. E6 and E7 oncoproteins expressed by HPV are known to inactivate tumor suppressor proteins p53 and pRb, respectively. Tanshinone IIA (Tan IIA) is a diterpenoid naphthoquinone found in the traditional Chinese medicine Danshen (Salvia sp.). Tan IIA has been shown to possess anti-tumor activity against several cancer types. In this study we show that Tan IIA potently inhibited proliferation of the human cervicalcancer CaSki, SiHa, HeLa and C33a cells. Mechanistically in HPV positive CaSki cells, Tan IIA was found to (i) downregulate expression of HPV E6 and E7 genes and modulate associated proteins E6AP and E2F1, (ii) cause S phase cell cycle arrest, (iii) induce accumulation of p53 and alter expression of p53-dependent targets, (iv) modulate pRb and related proteins, and (v) cause p53-mediated apoptosis by moderating Bcl2, Bax, caspase-3, and PARP cleavage expressions. In vivo, Tan IIA resulted in over 66% reduction in tumor volume of cervicalcancer xenograft in athymic nude mice. Tan IIA treated tumor tissues had lower expression of proliferation marker PCNA and changes in apoptosis targets were in agreement with in vitro studies, further confirming reduced proliferation and involvement of multiple targets behind anti-cancer effects. This is the first demonstration of Tan IIA to possess significant anti-viral activity by repressing HPV oncogenes leading to inhibition of cervicalcancer. Together, our data suggest that Tan IIA can be exploited as a potent therapeutic agent for the prevention and treatment of cervical and other HPV-related cancers. PMID:25304375

Aberrant miRNA expression is well recognized as an important step in the development of cancer. Close to 70 microRNAs (miRNAs) have been implicated in cervicalcancer up to now, nevertheless it is unknown if aberrant miRNA expression causes the onset of cervicalcancer. One of the best ways to address this issue is through a multistep model of carcinogenesis. In the progression of cervicalcancer there are three well-established steps to reach cancer that we used in the model proposed here. The first step of the model comprises the gene changes that occur in normal cells to be transformed into immortal cells (CIN 1), the second comprises immortal cell changes to tumorigenic cells (CIN 2), the third step includes cell changes to increase tumorigenic capacity (CIN 3), and the final step covers tumorigenic changes to carcinogenic cells. Altered miRNAs and their target genes are located in each one of the four steps of the multistep model of carcinogenesis. miRNA expression has shown discrepancies in different works; therefore, in this model we include miRNAs recording similar results in at least two studies. The present model is a useful insight into studying potential prognostic, diagnostic, and therapeutic miRNAs. PMID:25192291

Fluorescent molecular probes offer a potential for early cancer detection. Indocyanine green (ICG) is an FDAapproved near-infrared (NIR) fluorescent dye used in ophthalmic angiography and assessment of cardiac and hepatic functions. However, clinical applications of ICG remain very limited due to its rapid clearance from vascular circulation, unstable optical properties, non-specific interactions with plasma proteins, and inability for localized targeting.

Human papillomavirus (HPV) infection has been firmly established as a central and necessary cause of invasive cervicalcancer and it has been etiologically linked to other anogenital (vulva, vagina, anus and penis) and head and neck cancers, particularly oropharyngeal. Although being rare, the incidence of some of these cancers in some countries has increased in the last decades. HPV-related anogenital tumors share many risk factors with cervicalcancer. The HPV aetiological contribution differs in each anatomical location reflecting differences in the natural history and viral tissue tropism. The highest prevalence of HPV DNA in cancers other than cervix has been described for anal, followed by vagina, penile and vulvar cancers. HPV16 has been described as the most common type detected in all cancer sites with different contributions being the highest in anal carcinoma (around 80% of HPV DNA positive anal cancers) and the lowest in vaginal cancers with a contribution similar to that found in cervicalcancers (around 60%). Current HPV vaccines have already demonstrated their efficacy in preventing anogenital pre-neoplastic lesions caused by vaccine HPV types. HPV-based prevention tools like HPV vaccination and to a lesser extend screening (e.g. for anal cancer) can be useful measures for reducing the burden of these anogenital cancers. PMID:25455637

The high cervicalcancer mortality rate among Latinas compared with other ethnic groups in the United States is of major concern. Latina women are almost twice as likely to die from cervicalcancer as non-Hispanic white women. To improve Latina cervicalcancer screening rates, interventions have been developed and tested. This systematic review…

BackgroundCervicalcancer screening guidelines were created to help healthcare professionals in appropriate screening utilizing the PAP test. However, significant variation in cervicalcancer screening among primary care physicians has been noted. Knowledge of the awareness of and adherence to cervicalcancer screening guidelines by primary care physicians will help determine how best to disseminate and educate these physicians regarding the

Investigated college students' knowledge of the relationship between human papillomavirus (HPV) and cervicalcancer. Few students knew what HPV was. Most of the females who had been screened knew that a Pap smear could detect HPV and cervicalcancer. Over half of the students did not realize the link between HPV and cervicalcancer. Students…

At the beginning of the 21st century hypopharynx and cervical esophagus cancer represents a major issue for all countries of the world. The epidemiology of the hypopharynx and cervical esophagus cancer deals with the spread of the disease in human population in regards to sex, age, profession, time and space, as well as risk factors that contribute to these phenomena. The main goal is to investigate the causes and the factors involved in the development of the tumors at the pharyngo–esophageal junction, knowledge that contributes to latest therapeutic assessment through interdisciplinary collaboration (E.N.T. surgeon, general surgeon, radiation oncologist, chemotherapist, nutritionist). The epidemiology of the hypopharynx and cervical esophagus cancer includes three major areas of interest: descriptive (the study of the spread in mass population), analytical (the study of causal risk factors on the disease) and experimental (that verifies by experiments on animals the prior identified hypothesis). PMID:21254737

In this treatment planning study, the potential benefits of a rotating shield brachytherapy (RSBT) technique based on a partially-shielded electronic brachytherapy source were assessed for treating cervicalcancer. Conventional intracavitary brachytherapy (ICBT), intracavitary plus supplementary interstitial (IS+ICBT), and RSBT treatment plans for azimuthal emission angles of 180° (RSBT-180) and 45° (RSBT-45) were generated for five patients. For each patient, high-risk clinical target volume (HR-CTV) equivalent dose in 2 Gy fractions (EQD2) (?/? = 10 Gy) was escalated until bladder, rectum, or sigmoid colon tolerance EQD2 values were reached. External beam radiotherapy dose (1.8 Gy × 25) was accounted for, and brachytherapy was assumed to have been delivered in 5 fractions. IS+ICBT provided a greater HR-CTV D90 (minimum EQD2 to the hottest 90%) than ICBT. D90 was greater for RSBT-45 than IS+ICBT for all five patients, and greater for RSBT-180 than IS+ICBT for two patients. When the RSBT-45/180 plan with the lowest HR-CTV D90 that was greater than the D90 the ICBT or IS+ICBT plan was selected, the average (range) of D90 increases for RSBT over ICBT and IS+ICBT were 16.2 (6.3-27.2)and 8.5 (0.03-20.16) Gy, respectively. The average (range) treatment time increase per fraction of RSBT was 34.56 (3.68-70.41) min over ICBT and 34.59 (3.57-70.13) min over IS+ICBT. RSBT can increase D90 over ICBT and IS+ICBT without compromising organ-at-risk sparing. The D90 and treatment time improvements from RSBT depend on the patient and shield emission angle.

Southeast Asian women have higher invasive cervicalcancer incidence rates and lower Pap testing frequencies than most other racial/ethnic groups in the United States. However, there is little information about the cervicalcancer screening behavior of Cambodian-American women. Cambodian residents of Seattle were surveyed in person during late 1997 and early 1998. The PRECEDE model was used to guide the development of items that assessed predisposing, reinforcing, and enabling factors associated with cervicalcancer screening participation. The estimated overall survey response was 72%. Four hundred thirteen women completed our questionnaire. Approximately one-quarter (24%) of the respondents had never had a Pap test, and over one-half (53%) had not been screened recently. The following variables were positively associated with a history of at least one Pap smear: younger age, greater number of years since immigration, belief about Pap testing for postmenopausal women, prenatal care in the United States, and physician recommendation. Women who believed in karma were less likely to have ever been screened for cervicalcancer than those who did not. Six variables independently predicted recent screening: age; beliefs about regular checkups, cervicalcancer screening for sexually inactive women, and the prolongation of life; having a female doctor; and a previous physician recommendation for Pap testing. The study findings indicate that culturally specific approaches might be effective in modifying the cervicalcancer screening behavior of immigrant women. Programs targeting Cambodian-Americans are likely to be more effective if they are multifaceted and simultaneously address predisposing, reinforcing, and enabling factors. PMID:10385145

Background To discover cancer specific DNA methylation markers, large-scale screening methods are widely used. The pharmacological unmasking expression microarray approach is an elegant method to enrich for genes that are silenced and re-expressed during functional reversal of DNA methylation upon treatment with demethylation agents. However, such experiments are performed in in vitro (cancer) cell lines, mostly with poor relevance when extrapolating to primary cancers. To overcome this problem, we incorporated data from primary cancer samples in the experimental design. A strategy to combine and rank data from these different data sources is essential to minimize the experimental work in the validation steps. Aim To apply a new relaxation ranking algorithm to enrich DNA methylation markers in cervicalcancer. Results The application of a new sorting methodology allowed us to sort high-throughput microarray data from both cervicalcancercell lines and primary cervicalcancer samples. The performance of the sorting was analyzed in silico. Pathway and gene ontology analysis was performed on the top-selection and gives a strong indication that the ranking methodology is able to enrich towards genes that might be methylated. Terms like regulation of progression through cell cycle, positive regulation of programmed cell death as well as organ development and embryonic development are overrepresented. Combined with the highly enriched number of imprinted and X-chromosome located genes, and increased prevalence of known methylation markers selected from cervical (the highest-ranking known gene is CCNA1) as well as from other cancer types, the use of the ranking algorithm seems to be powerful in enriching towards methylated genes. Verification of the DNA methylation state of the 10 highest-ranking genes revealed that 7/9 (78%) gene promoters showed DNA methylation in cervical carcinomas. Of these 7 genes, 3 (SST, HTRA3 and NPTX1) are not methylated in normal cervix tissue. Conclusion The application of this new relaxation ranking methodology allowed us to significantly enrich towards methylation genes in cancer. This enrichment is both shown in silico and by experimental validation, and revealed novel methylation markers as proof-of-concept that might be useful in early cancer detection in cervical scrapings. PMID:19025626

Although significant advances have recently been made in the diagnosis and treatment of cervical carcinoma, the long-term survival rate for advanced cervicalcancer remains low. Therefore, an urgent need exists to both uncover the molecular mechanisms and identify potential therapeutic targets for the treatment of cervicalcancer. MicroRNAs (miRNAs) have important roles in cancer progression and could be used as either potential therapeutic agents or targets. miR-506 is a component of an X chromosome-linked miRNA cluster. The biological functions of miR-506 have not been well established. In this study, we found that miR-506 expression was downregulated in approximately 80% of the cervicalcancer samples examined and inversely correlated with the expression of Ki-67, a marker of cell proliferation. Gain-of-function and loss-of-function studies in human cervicalcancer, Caski and SiHa cells, demonstrated that miR-506 acts as a tumor suppressor by inhibiting cervicalcancer growth in vitro and in vivo. Further studies showed that miR-506 induced cell cycle arrest at the G1/S transition, and enhanced apoptosis and chemosensitivity of cervicalcancercell. We subsequently identified Gli3, a hedgehog pathway transcription factor, as a direct target of miR-506 in cervicalcancer. Furthermore, Gli3 silencing recapitulated the effects of miR-506, and reintroduction of Gli3 abrogated miR-506-induced cell growth arrest and apoptosis. Taken together, we conclude that miR-506 exerts its anti-proliferative function by directly targeting Gli3. This newly identified miR-506/Gli3 axis provides further insight into the pathogenesis of cervicalcancer and indicates a potential novel therapeutic agent for the treatment of cervicalcancer. PMID:24608427

... 2011. College of American Pathologists. For use and reproduction by patients and CAP members only. Cervical dysplasia. Normal cervicalcells. (continued from previous page) What characterizes cervical dysplasia? ...

Because of the complexity of cervicalcancer prevention guidelines, clinicians often fail to follow best-practice recommendations. Moreover, existing clinical decision support (CDS) systems generally recommend a cervical cytology every three years for all female patients, which is inappropriate for patients with abnormal findings that require surveillance at shorter intervals. To address this problem, we developed a decision tree-based CDS system that integrates national guidelines to provide comprehensive guidance to clinicians. Validation was performed in several iterations by comparing recommendations generated by the system with those of clinicians for 333 patients. The CDS system extracted relevant patient information from the electronic health record and applied the guideline model with an overall accuracy of 87%. Providers without CDS assistance needed an average of 1 minute 39 seconds to decide on recommendations for management of abnormal findings. Overall, our work demonstrates the feasibility and potential utility of automated recommendation system for cervicalcancer screening and surveillance. PMID:25368505

Development of HPV-associated cancers not only depends on efficient negative regulation of cell cycle control that supports the accumulation of genetic damage, but also relies on immune evasion that enable the virus to go undetected for long periods of time. In this way, HPV-related tumors usually present MHC class I down-regulation, impaired antigen-processing ability, avoidance of T-cell mediated killing, increased immunosuppression due to Treg infiltration and secrete immunosuppressive cytokines. Thus, these are the main obstacles that immunotherapy has to face in the treatment of HPV-related pathologies where a number of different strategies have been developed to overcome them including new adjuvants. Although antigen-specific immunotherapy induced by therapeutic HPV vaccines was proved extremely efficacious in pre-clinical models, its progression through clinical trials suffered poor responses in the initial trials. Later attempts seem to have been more promising, particularly against the well-defined precursors of cervical, anal or vulvar cancer, where the local immunosuppressive milieu is less active. This review focuses on the advances made in these fields, highlighting several new technologies (such as mRNA vaccine, plant-derived vaccine). The most promising immunotherapies used in clinical trials are also summarized, along with integrated strategies, particularly promising in controlling tumor metastasis and in eliminating cancercells altogether.After the early promising clinical results, the development of therapeutic HPV vaccines need to be implemented and applied to the users in order to eradicate HPV-associated malignancies, eradicating existing perception (after the effectiveness of commercial preventive vaccines) that we have already solved the problem. PMID:24667138

Infection by an oncogenic human papillomavirus (HPV), in particular HPV16 and 18, is a high risk factor for developing cervicalcancer; however, viral infection alone is not sufficient for cancer progression. Autophagy is hypothesized to be an important process during carcinogenesis. The aim of the present study was to investigate the association between autophagy and high-risk HPV (hrHPV) infection in human cervical squamous cell carcinomas (SCCs), and to analyze the clinical significance of this association. Quantum dot (QD)-based immunofluorescence histochemistry was used to detect the expression of autophagy markers, Beclin-1 and microtubule-associated proteins 1A/1B light chain 3B (LC3B) proteins, in 104 cases of cervicalcancer (including 80 SCCs and 24 adenocarcinomas) and 20 normal cervical tissues. hrHPV (HPV16/18) infection was detected by QDs based fluorescence in situ hybridization in cervicalcancers. The results revealed that the expression levels of Beclin-1 and LC3B were significantly lower in cervicalcancercells when compared with those of normal cervical squamous epithelial cells, and were found to negatively correlate with hrHPV infection. The expression levels of Beclin-1 and LC3B were not associated with age, tumor grade, tumor stage, tumor node metastasis stage or lymph node metastasis. However, a positive correlation was identified between Beclin-1 and LC3B protein expression. In addition, the absence of autophagy in combination with hrHPV infection may accelerate the progression of cervical SCC. In conclusion, decreased expression of Beclin-1 and LC3B may be important in cervical carcinogenesis. The hrHPV-host cell interaction may inhibit autophagy, which may aid virus duplication and infection, as well as cervicalcancer development. PMID:25202355

In this phase III trial, women with metastatic, recurrent, or persistent cervicalcancer that cannot be treated with surgery and/or radiation therapy will be randomly assigned to one of four treatment groups: paclitaxel plus cisplatin, paclitaxel plus topotecan, or either of these combinations with the addition of bevacizumab.

The purpose of this study was to gather information on the prevalence of pap smear testing among Vietnamese women and to identify predictive factors that influence women to engage in early cervicalcancer detection behavior. One hundred and forty-one (141) Vietnamese women ages 18 years and older and living in Western Massachusetts were surveyed by telephone. The overall socioeconomic status

Introduction Chinese American women have high rates of invasive cervicalcancer, compared to the general population. However, little is known about the Pap testing behavior of ethnic Chinese immigrants. Methods We conducted a community-based survey of Chinese immigrants living in Seattle, Washington, during 1999. Two indicators of cervicalcancer screening participation were examined: at least one previous Pap smear and Pap testing in the last 2 years. Results The overall estimated response rate was 64%, and the cooperation rate was 72%. Our study sample for this analysis included 647 women. Nearly one quarter (24%) of the respondents had never had a Pap test, and only 60% had been screened recently. Factors independently associated with cervicalcancer screening use included marital status, housing type, and age at immigration. Conclusion Our findings confirm low levels of cervicalcancer screening among Chinese immigrants to North America. Culturally and linguistically appropriate Pap testing intervention programs for less acculturated Chinese women should be developed, implemented, and evaluated. PMID:16228798

Background and Objective: In less than 2 decades, laparoscopy has contributed to modification in the management of early cervicalcancer patients, and all comparisons between open and laparoscopic-based radical operations showed an identical oncological outcome. The aim of this study is to describe surgical instrumentations and technique to perform total microlaparoscopy radical hysterectomy in early cervicalcancer patients and report our preliminary results in terms of operative time and perioperative outcomes. Methods: Between January 1, 2012, and March 25, 2012, 4 consecutive early cervicalcancer patients were enrolled in this study. Results: We performed 3 type B2 and 1 type C1-B2 total microlaparoscopy radical hysterectomy, and in all cases concomitant bilateral salpingo-oophorectomy and pelvic lymphadenectomy were carried out. Median operative time was 165 minutes (range: 155 to 215) (mean: 186), and median estimated blood loss was 30 mL (range: 20 to 50). Median number of pelvic lymph nodes removed was 12 (range: 11 to 15). All procedures were completed without 5-mm port insertion and without conversion. No intraoperative or early postoperative complications were reported. Conclusions: This report suggests a role of microlaparoscopy in the surgical management of early cervicalcancer with adequate oncological results, superimposable operative time, and perioperative outcomes with respect to standard laparoscopy. PMID:23743381

Patients with locally advanced cervicalcancer who received gemcitabine (Gemzar®) both as part of initial treatment and as part of therapy following primary treatment had improved survival compared with patients whose treatment did not include gemcitabine, according to findings presented at the 2009 ASCO meeting in Orlando.

We enrolled 85 patients with invasive cervicalcancer and collected cervicovaginal lavage samples at each clinical visit for diagnosis, staging, treatment, and follow-up. Lavage samples were tested by L1 consensus polymerase chain reaction for human papillomavirus (HPV). Results were compared with HPV demonstrated in tumor tissue and the clinical status at time of sample collection. Sensitiv- ity and specificity of

To examine the hypothesis that the pattern of cervicalcancer is changing data on women presenting with the disease over 34 years were studied retrospectively. During 1953-86, 2628 women with cervicalcancer were referred to a large tertiary referral hospital in Sydney; 418 were aged 35 or less. During the period of review the proportion of young women with the disease increased from under 9% in the 1950s and 1960s to about 25% in the 1970s and 1980s; a similar but less pronounced trend was apparent for the whole of New South Wales in the 1970s and 1980s. The prevalence of less common morphological types of cervicalcancer increased throughout the period, particularly in the young. Pelvic lymph node metastases were identified in younger patients with stage Ib and IIa tumours more commonly in the later years of the study, suggesting that the disease was becoming more severe. Overall rates of recurrence improved over time, but an apparent increase in early recurrences was observed in young patients with Ib and IIa tumours and without nodal disease. The results suggest that the clinical and pathological behaviour of cervicalcancer changed over the period of review. PMID:2493898

Cervicalcancer is a diagnosis that has a profound psychosocial impact, constituting a physical and emotional crisis for patients as well as family. In general, research indicates that the choice of treatment and the stage of the disease are instrumental in determining the psychosocial adjustment. Disruptions are likely to occur in self-esteem,…

The purpose of this study was to test the hypothesis that follow-up rates for women with abnormal cervicalcancer screening results vary by age, ethnicity, and initial screening results in California's Breast and CervicalCancer Control Program. The sample consisted of women in the screening program who received an abnormal cervical screening result (N = 1,738). Bivariate and logistic regression

The knowledge that the persistent infection with high-risk (HR) human papillomavirus (HPV) is the etiological factor in the development of cervicalcancer has led to the development of the HPV DNA detection methods as well as the prophylactic vaccine against the most common HR-HPV types, HPV 16 and 18. Despite HPV vaccination, cervicalcancer screening will remain the main preventive measure for both vaccinated and non-vaccinated women, but the nature of screening and management of women with cervical disease is being adapted to the new technologies. Although, HPV DNA detection is more sensitive that cytology, its specificity is lower, since most HPV infections are transient. Therefore, other methods are considered to improve the management of women with cervical disease. Typing of HPV DNA and viral load measurements are still used for research purposes only. Detection of viral oncogene E6/E7 transcripts, which is the marker of the productive infection, is a promising tool for follow-up of HPV DNA-positive women. The detection of p16INK4a over-expression, as an indirect test of E6/E7 expression, is used for confirmation of cervical neoplasia. Despite the lack of standardization, the detection of p16INK4a is useful in clinical settings, however its reproducibility in the management of low-grade and borderline cases is low. Future perspectives include the determination of the methylation status of several cellular genes that could predict the progression of the disease. PMID:20698164

A new therapeutic approach of looking at the expression of glucose-regulated protein (GRP) 58 as an indication of cisplatin sensitivity may eradicate fruitless treatment and side effects in patients with cervicalcancer. Thymoquinone, the bioactive compound in Nigella sativa, has been reported to have an antiproliferative effect on cervicalcancercells. This study compared the cytotoxic effects of cisplatin, a drug commonly used in the treatment of cervicalcancer, and thymoquinone in cervicalcancer (HeLa and SiHa) cell lines by 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and measured GRP58 expression in the cells by quantitative real-time polymerase chain reaction and Western blotting. Cisplatin had higher antiproliferative activity towards the cervicalcancercell lines than thymoquinone in a dose-dependent and time-dependent manner. However, cisplatin was more toxic to normal 3T3 and Vero cell lines than thymoquinone. The half maximal inhibitory concentration (IC50) of cisplatin in HeLa and SiHa cells at 72 hours was 13.3±2.52 ?M and 19.5±2.12 ?M, respectively. Meanwhile, the IC50 of thymoquinone in HeLa and SiHa cells was 29.57±5.81 ?M and 23.41±1.51 ?M, respectively (P<0.05). A significant correlation was found between the cytotoxicity of cisplatin and expression of GRP58, but this relationship was not significant for thymoquinone. Therefore, the response of cervicalcancercells to cisplatin can be predicted on the basis of GRP58 expression. PMID:25143744

The cell of origin of uterine cervicalcancer was studied by using culture, enzyme histochemistry and heterotransplantation. Twenty-seven epidermoid carcinomas (8 large cell keratinizing squamous, 12 large cell nonkeratinizing squamous and 7 small cell nonkeratinizing squamous) and 2 adenocarcinomas of the uterine cervix were placed in culture. An outgrowth of carcinoma cells in vitro was observed in 22 of 29 cases: 6 keratinizing, 8 large cell nonkeratinizing and 6 small cell nonkeratinizing carcinomas and 2 adenocarcinomas. The squamous carcinomas showed a squamous-cell outgrowth pattern, except for one large cell nonkeratinizing and three small cell nonkeratinizing carcinomas that showed a glandular-cell outgrowth pattern. One of three keratinizing carcinomas was transplantable into the subcutis of BALB/c nude mice, producing keratinizing tumors; three of six large cell and one of three small cell nonkeratinizing carcinomas reproduced themselves, while the other two small cell carcinomas produced poorly differentiated adenocarcinomas in mice. The transplanted adenocarcinoma produced a well-differentiated adenocarcinoma resembling the original tumor. Small cell carcinomas and adenocarcinomas contained a heat-stable, L-phenylalanine-sensitive alkaline phosphatase. These results suggest that many uterine cervicalcancers originate from the reserve cell. PMID:3425154

Well-run screening programs for cervicalcancer in the population at risk have been shown to result in a sharp decrease in the incidence and mortality of cervicalcancer in a number of large populations. Expression patterns of a recently identified biomarker family, microRNA, appear to be characteristic of tumor type and developmental origin. Several tumors have been reported to actively release exosomes carrying microRNAs. The present study has determined the association of microRNAs with cervicalcancer-derived exosomes. The cervicalcancer-derived exosomes were enriched in the cervicovaginal lavages specimens and the abundance of exosomes and exosomal microRNAs was detected by electron microscopy, western blot analysis, RT-qPCR and microRNA target reporter vector. The microRNA-21 and microRNA-146a, which were up-regulated in cervicalcancer patients, were associated with the high levels of cervicalcancer-derived exosomes. In conclusion, we demonstrated the abundance of exosomes in the cervicovaginal lavage specimens of women with cervicalcancer. Furthermore, our results indicated that abnormally high levels of microRNA-21 and microRNA-146a existed in the cervicalcancer-derived exosomes and the two microRNAs were functional in 293T cells. PMID:24406730

The human cervix is a tissue target of sex steroid hormones as estradiol (E2) which exerts its action through of the estrogen receptors alpha and beta (ER-? and ER-?). In this study we investigated the expression of ER-? and ER-? in human invasive cervical carcinomas using immunohistochemistry and RT-PCR analyses and compared with that observed in the corresponding normal tissue. The results show nuclear expression of ER-? mainly in the first third of normal cervical epithelium, however, decreased or absent expression were present in invasive cervical carcinoma, indicating that expression of ER-? is lost in cervicalcancer. Nevertheless, by RT-PCR we were able to demonstrate mRNA expression of ER-? in invasive cervical tissues. These results suggest that loss of ER-? could be due to a mechanism of post-transcriptional and/or post-translational regulation of its gene during the progression to invasive carcinoma. On the other hand, ER-? was expressed in normal cervix with an expression pattern similar to ER-?. In addition to its nuclear localization, cytoplasmic immunoreaction of ER-? was present in the epithelium of invasive cervical carcinomas, suggesting an association between cytoplasmic ER-? expression and invasive phenotype in the cervical tumors. In summary, the results show that the cervical malignant cells tend to loss the ER-? but maintain the ER-? actively expressed. Loss of expression of ER-? in neoplastic tissue suggests that the estrogenic effects could be conducted through the ER-? in human neoplastic cervical tissue. More detailed studies are needed to confirm this suggestion and to determine the role of ER-? in cervicalcancer. PMID:23923078

This chapter will review the current modalities available to the clinician to screen for premalignant and malignant cervical lesions, which cast a broad net. The majority who test positive are not destined to suffer from or die from cervicalcancer. Many who undergo screening and are triaged are young and subsequently face a number of aggressive and destructive therapies. This calls into question whether higher-risk patients should be managed more aggressively than an average-risk patient represented in the study population used to craft the guidelines. PMID:24662770

MicroRNAs (miRNAs) are a class of single-stranded, non-coding RNAs of about 22 nucleotides in length. Increasing evidence implicates miRNAs may function as oncogenes or tumor suppressors. Here we showed that miR-107 directly targeted MCL1 and activated ATR/Chk1 pathway to inhibit proliferation, migration and invasiveness of cervicalcancercells. Moreover, we found that MCL1 was frequently up-regulated in cervicalcancer, and knockdown of MCL1 markedly inhibited cancercell proliferation, migration and invasion, whereas ectopic expression of MCL1 significantly enhances these properties. The restoration of MCL1 expression can counteract the effect of miR-107 on the cancercells. Together, miR-107 is a new regulator of MCL1, and both miR-107 and MCL1 play important roles in the pathogenesis of cervicalcancer. We have therefore identified a mechanism for ATR/Chk1 pathway which involves an increase in miR-107 leading to a decrease in MCL1. Correspondingly, our results revealed that miR-107 affected ATR/Chk1 signalling and gene expression, and implicated miR-107 as a therapeutic target in human cervicalcancer. We also demonstrated that taxol attenuated migration and invasion in cervicalcancercells by activating the miR-107, in which miR-107 play an important role in regulating the expression of MCL1. Elucidation of this discovered MCL1 was directly regulated by miR-107 will greatly enhance our understanding of the mechanisms responsible for cervicalcancer and will provide an additional arm for the development of anticancer therapies. PMID:25386925

Cytotoxic T lymphocytes (CTL) specific against autologous human cervicalcancercells were generated in vitro from peripheral blood leukocytes (PBL) from four patients with non-keratinized epidermoid carcinoma. For this purpose, these patients' PBL were co-cultured for 28 days either with IL-2 or a mixture of IL-2, IFN-gamma and TNF-alpha in the presence of autologous tumour cells (ATC). Our results showed that these CTL were highly cytotoxic for ATC, weakly cytotoxic for heterologous cervicalcancer tumour cells, and not cytotoxic for carcinoma cell lines, normal cervix cells nor autologous PBL. Proliferation and cytotoxicity against ATC were greater when the PBL were activated with the three cytokines. These CTL had a CD4:CD8 ratio of 1:1, were CD16- and CD45RO+ and their killing activity was inhibited by antibodies against CD3, CD8 and MHC-class I but not by antibodies against CD4, CD16 or HLA-class II. The possibility of generating specific CTL in long term cultures for cervicalcancer therapy is also discussed. PMID:8589277

Papillary thyroid cancer (PTC) is the most rapidly increasing endocrine malignancy worldwide. Although less aggressive than the majority malignancies, PTC exhibits extensive cervical lymph node metastasis in early stage of PTC. However, the underlying molecular mechanism of this early-metastasis remains unknown. Toll like receptors (TLRs) constitute a crucial component of the innate immune response to bacterial and viral pathogens. Emerging evidence suggests that TLRs play important roles in cancer progression, invasion and immune evasion, whereas whether TLRs have any role in PTC remains to be clarified. In this study, we found that TLR3 was present in both PTC specimen and various thyroid cancercell lines. Further IHC analysis of 63 PTC patients revealed that TLR3 expression was associated with cervical metastasis, but not correlated with patients’ TNM staging, extrathyroidal invasion. In addition, TLR3 promoted migration of K1 cells in vitro. Activation of TLR3 increased cancer stem cell marker and migration promoting CD44 expression in vitro, indicating that TLR3 might promote metastasis of PTC via modulating CD44 expression. Taken together, our data revealed that TLR3 is correlated with cervical metastasis of PTC and might be an essential prognostic indicator and target for PTC metastasis. PMID:25664012

In locally advanced cervicalcancer, 18F-fluorodeoxyglucose (FDG) positron emission tomography – computed tomography (PET/CT) has become important in the initial evaluation of disease extent. It is superior to other imaging modalities for lymph node status and distant metastasis. PET-defined cervical tumor volume predicts progression-free and overall survival. Higher FDG uptake in both primary and regional lymph nodes is strongly predictive of worse outcome. FDG-PET is useful for assessing treatment response 3 months after completing concurrent chemo-radiotherapy (CRT) and predicting long-term survival, and in suspected disease recurrence. In the era of image-guided adaptive radiotherapy, accurately defining disease areas is critical to avoid irradiating normal tissue. Based on additional information provided by FDG-PET, radiation treatment volumes can be modified and higher doses to FDG-positive lymph nodes safely delivered. FDG-PET/CT has been used for image-guided brachytherapy of FDG-avid tumor volume, while respecting low doses to bladder and rectum. Despite survival improvements due to CRT in cervicalcancer, disease recurrences continue to be a major problem. Biological rationale exists for combining novel non-cytotoxic agents with CRT, and drugs targeting specific molecular pathways are under clinical development. The integration of these targeted therapies in clinical trials, and the need for accurate predictors of radio-curability is essential. New molecular imaging tracers may help identifying more aggressive tumors. 64Cu-labeled diacetyl-di(N(4)-methylthiosemicarbazone) is taken up by hypoxic tissues, which may be valuable for prognostication and radiation treatment planning. PET/CT imaging with novel radiopharmaceuticals could further impact cervicalcancer treatment as surrogate markers of drug activity at the tumor microenvironment level. The present article reviews the current and emerging role of PET/CT in the management of cervicalcancer. PMID:23549376

. Detection 1) PAP smear Â§ Fluid-based test allows for the separation of cervicalcells for more accurate the results of the Pap #12;11/12/12 5 The transformation zone is the critical area to sample when performing

Epigenetic remodeling of cell adhesion genes is a common phenomenon in cancer invasion. This study aims to investigate global methylation of cell adhesion genes in cervical carcinogenesis and to apply them in early detection of cancer from cervical scraping. Genome-wide methylation array was performed on an investigation cohort, including 16 cervical intraepithelial neoplasia 3 (CIN3) and 20 cervicalcancers (CA) versus 12 each of normal, inflammation and CIN1 as controls. Twelve members of clustered proto-cadherin (PCDH) genes were collectively methylated and silenced, which were validated in cancercells of the cervix, endometrium, liver, head and neck, breast, and lung. In an independent cohort including 107 controls, 66 CIN1, 85 CIN2/3, and 38 CA, methylated PCDHA4 and PCDHA13 were detected in 2.8%, 24.2%, 52.9%, and 84.2% (P cervical scraping had a sensitivity, specificity, positive predictive value, and negative predictive value of 74.8%, 80.3%, 73%, and 81.8%, respectively. Testing of this combination from cervical scraping is equally sensitive but more specific than human papillomavirus (HPV) test in diagnosis of CIN2 or more severe lesions. The study disclosed a collective methylation of PCDH genes in cancer of cervix and other sites. At least two of them can be promising diagnostic markers for cervicalcancer noninferior to HPV. PMID:25418975

Purpose: Preclinical data indicate a synergistic effect on apoptosis between irradiation and recombinant human (rh) tumor necrosis factor-related apoptosis inducing ligand (TRAIL), making the TRAIL death receptors (DR) interesting drug targets. The aim of our study was to analyze the expression of DR4, DR5, and TRAIL in cervicalcancer and to determine their predictive and prognostic value. Methods and Materials: Tissue microarrays were constructed from tumors of 645 cervicalcancer patients treated with surgery and/or (chemo-)radiation between 1980 and 2004. DR4, DR5, and TRAIL expression in the tumor was studied by immunohistochemistry and correlated to clinicopathological variables, response to radiotherapy, and disease-specific survival. Results: Cytoplasmatic DR4, DR5, and TRAIL immunostaining were observed in cervical tumors from 99%, 88%, and 81% of the patients, respectively. In patients treated primarily with radiotherapy, TRAIL-positive tumors less frequently obtained a pathological complete response than TRAIL-negative tumors (66.3% vs. 79.0 %; in multivariate analysis: odds ratio: 2.09, p {<=}0.05). DR4, DR5, and TRAIL expression were not prognostic for disease-specific survival. Conclusions: Immunostaining for DR4, DR5, and TRAIL is frequently observed in the cytoplasm of tumor cells in cervicalcancer patients. Absence of TRAIL expression was associated with a higher pathological complete response rate to radiotherapy. DR4, DR5, or TRAIL were not prognostic for disease-specific survival.

The newly gained knowledge of the viral etiology in cervical carcinogenesis has prompted industrial interests in developing virology-based tools for cervicalcancer prevention. Due to the long incubation period from viral infection to developing an invasive cancer, a process whose outcome is influenced by numerous life-style and genetic factors, the true efficacy of the genotype-specific human papillomavirus (HPV) vaccines in cervicalcancer prevention cannot be determined for another 30 years. Most HPV DNA test kits designed to replace the traditional Papanicolaou (Pap) smears for precancer detection lack the analytical sensitivity and specificity to comprehensively detect all potentially carcinogenic HPVs and to perform reliable genotyping. The authors implemented the classic nested PCR and Sanger DNA-sequencing technology for routine HPV testing. The results showed a true negative HPV PCR invariably indicates the absence of precancerous cells in the cytology samples. However, 80.5% of single positive HPV-16 tests and 97.3% of single positive HPV-18 tests were associated with a negative or a largely self-reversible Pap cytology. Routine sensitive and reliable HPV type-specific or perhaps even variant-specific methods are needed to address the issues of persistence of HPV infection if a virology-based primary cervical screen is used to replace the Pap cytology screening paradigm. PMID:25279452

More than 90% of cancer mortalities are due to cancer that has metastasized. Therefore, it is crucial to intensify research on metastasis formation and therapy. Here, we describe for the first time the metastasizing ability of the human cervicalcancercell line C33A in athymic nude mice after subcutaneous implantation of tumor cells. In this model, we demonstrated a steady progression of lumbar and renal lymph node metastases during tumor development. Besides predominantly occurring lymphatic metastases, we visualized the formation of hematogenous metastases utilizing red fluorescent protein (RFP) expressing C33A-RFP cells. RFP positive cancercells were found migrating in blood vessels and forming micrometastases in lungs of tumor-bearing mice. Next, we set out to analyze the influence of oncolytic virotherapy in the C33A-RFP model and demonstrated an efficient virus-mediated reduction of tumor size and metastatic burden. These results suggest the C33A-RFP cervicalcancer model as a new platform to analyze cancer metastases as well as to test novel treatment options to combat metastases. PMID:24887184

It is presently the right time for clarifying human papillomavirus (HPV)-associated cellular immunity and clinical implications before global HPV vaccination programs begin. Infection with oncogenic HPV associates with the progression of cervical neoplasia. Both cellular and humoral immune responses are essential for the clearance of HPV-associated cervical lesions. There is increasing evidence that the immune system plays a pivotal role in determining the outcome of HPV infection. Viruses and associated neoplastic cells are proposed to have evolved mechanisms to avoid immune attack. T-cell-mediated immune responses against oncogenic HPV are believed to play a central role in cervical carcinogenesis. The presence of HPV-specific cytotoxic T lymphocytes (CTL) in a majority of human cervicalcancer patients provides an approach for further study of their functional role in modulating this malignancy. Tumor-infiltrating lymphocytes (TIL) develop as manifestations of the recognition and defense against malignant cells by the host immune system. Cancercells may overcome immune surveillance, either by downregulating the proliferation of HPV-specific CTL, or altering the effector compositions of immune cells against HPV infections. TIL in the tumor microenvironment can be functionally inhibited and lose the ability of clonal proliferation as a result of depressed expression of IL-2Ralpha. The upregulation of inhibitory signaling relates to the modulation of the virus- and/or tumor-specific immune responses. Alteration of host genetic susceptibility may also lead to abnormal immune response as a general genomic instability resulting from virus persistence. Induction of HPV-specific immune responses is anticipated as an intimate point for the treatment of cervical neoplasia. PMID:17441881

Cervicalcancers, a malignancy associated with oncogenic papilloma viruses, remain a major disease burden in the absence of effective implementation of preventive strategies. CD66(+) cells have previously been identified as a tumor-propagating subset in cervicalcancers. We investigated the existence, differentiation state, and neoplastic potential of CD66(+) cells in a precancer cell line harboring HPV31b episomes. The gene expression profile of CD66(high) cells overlaps with differentiated keratinocytes, neoplastic mesenchymal transition, cells of the squamocolumnar junction, and cervicalcancercell line-derived spheroids. There is elevated expression of DNMT1, Notch1, and the viral gene product E1?E4 in CD66(high) cells. Thus, CD66(high) cells, in the absence of differentiating signals, express higher levels of key regulators of keratinocytes stemness, differentiation, and the viral life cycle, respectively. We also find a striking association of neoplastic traits, including migration, invasion, and colony formation, in soft agar with CD66(high) cells. These properties and a distinct G2-M-enriched cell-cycle profile are conserved in cells from cervicalcancers. Principally, using a precancerous cell line, we propose that CD66(high) cells have an intermediate differentiation state, with a cellular milieu connected with both viral replication and neoplastic potential, and validate some key features in precancer lesions. Such pathophysiologically relevant systems for defining cellular changes in the early phases of the disease process provide both mechanistic insight and potential therapeutic strategies. Collectively, our data provide a rationale for exploring novel therapeutic targets in CD66(+) subsets during cancer progression. PMID:25267065

Cervical carcinoma is the second most prevalent type of malignancy in females worldwide. The crucial etiological factors involved in the development of cervical carcinoma include infection with the papillomavirus, and the structural or functional mutation of oncogenes and tumor suppressor genes. CD44 refers to a multifunctional family of type I transmembrane proteins. These proteins have been implicated in numerous biological processes, including cell adhesion, cell migration and metastasis. The present study examined the differences in the expression levels of ATP-binding cassette sub-family G member 2, CD24, CD44, CD133, cytokeratin (CK) 14 and CK19 between cervicalcancer tissues and corresponding normal non-tumor tissues by flow cytometry. Then, the CD44+ or CD44? cells from cervicalcancer tissues were sorted for identification and confirmation of differential expression by flow cytometry. The results demonstrated that the expression level of CD44 in cervicalcancer tissues was higher than in the corresponding non-tumor normal tissues (t=3.12; P=0.0102). Compared with the CD44? cells, the FOS-like antigen 1 (Fra-1), nestin, nuclear receptor subfamily 4, group A, member 2, OCT4 and p63 genes were highly expressed in CD44+ cells. The fold changes were 3.55, 3.55, 2.46, 2.87 and 2.56, respectively (P<0.05). However, BMI1 polycomb ring finger oncogene, ck5, tumor protein p53 and lactotransferrin genes exhibited low expression levels in CD44+ cells. It was verified by western blot analysis and flow cytometry that Fra-1 was highly expressed in CD44+ cells. Fra-1 was a potential target of miR-19a and miR-19b. The expression of miR-19a and miR-19b was downregulated by ~50% in CD44+ cells compared with CD44? cells. These findings suggested that CD44 dysregulated the activation of the Fra?1 gene. The interaction of Fra-1 and CD44 may therefore be important in cervical carcinoma. PMID:24604526

Objective To characterize the cervicalcancers diagnosed following a Pap-negative, high risk human papillomavirus (HPV)-positive (Pap?/HPV+) screen in routine clinical practice. Methods Using data from Kaiser Permanente Northern California, we investigated the cases of cervicalcancer diagnosed between January, 2003 through January, 2009 following Pap?/HPV+ screen. Two cervical specimens were routinely collected for cervicalcancer screening, one for conventional cytology and the other for high risk HPV testing using Hybrid Capture 2 (Qiagen). Results Forty-four women (median age at diagnosis = 44 years) were diagnosed with primary invasive cervicalcancer with a recent history of one or more Pap?/HPV+ screens. Twenty-six women had one Pap?/HPV+ screen preceding the diagnosis of cancer, 15 had two, and three had three. There were 16 squamous cancers, one small cellcancer, 24 adenocarcinomas, 2 adenosquamous carcinomas, and one case with separate invasive squamous and adenocarcinoma. FIGO Stage was IA in 11 women, IB in 31 women and IIA in 2 women. Treatment included a pelvic node dissection in 230, 2 (6.7%) of whom had positive nodes. Conclusions HPV testing contributes to early cervicalcancer diagnosis detection in women with negative Pap tests. Most women in this cohort have early stage, node negative, treatable and potentially curable disease. Adenocarcinoma predominated as might be expected because cytology misses these cancers and their precursors. The majority of cancers were diagnosed following a single Pap?/HPV+ screen, suggesting that effective triage to colposcopy of women with a Pap?/HPV+ screen would be preferable to retesting in one year as currently recommended. PMID:21276605

Cervicalcancer arises from cells localized in the ectoendocervical squamocolumnar junction of the cervix persistently infected with one of about 13 human papillomavirus (HPV) genotypes. The majority of HPV infections induces low grade squamous epithelial lesions that in more than 90% of cases spontaneously regress and in about 10% eventually progress to high grade lesions and even less frequently evolve to invasive cancer. Tumor progression is characterized by (1) increased expression of E6 and E7 genes of high risk HPVs, known to bind to and inactivate p53 and pRb oncosuppressors, respectively; (2) integration of viral DNA into host genome, with disruption of E2 viral genes and host chromosomal loci; and (3) molecular alterations of key regulators of cell cycle. Molecular markers with high sensitivity and specificity in differentiating viral infections associated with cellular abnormalities with high risk of progression are strongly needed for cervicalcancer screening and triage. This review will focus on the analysis of clinical validated or candidate biomarkers, such as HPV DNA, HPV E6/E7 mRNA, HPV proteins, p16(INK4a) and Ki67, TOP2A and MCM2 cellular factors, and DNA methylation profiles, which will likely improve the identification of premalignant lesions that have a high risk to evolve into invasive cervicalcancer. PMID:24383054

Background: Cervicalcancer is the most common genital cancer and one of the leading causes of death among female population. Fortunately, this cancer is preventable by screening for premalignant lesions but this is rarely provided and hardly utilised. We assessed the knowledge, attitude and utilisation of cervicalcancer screening among market women in Sabon Gari, Zaria. Materials and Methods: This was a cross-sectional study to evaluate the knowledge, attitude and practice of cervicalcancer screening among market women. A total of 260 women were administered with questionnaires which were both self and interviewer administered. These were analysed using SPSS version 11. Results: Respondents exhibited a fair knowledge of cervicalcancer and cervicalcancer screening (43.5%); however, their knowledge of risk factors was poor. There was generally good attitude to cervicalcancer screening (80.4%), but their level of practice was low (15.4%). Conclusions: There was a fair knowledge of cervicalcancer and cervicalcancer screening among Nigerian market women in this study, their practice of cervicalcancer screening was poor. PMID:24403709

Recent advances in the surgical management of early cervicalcancer, including abdominal, laparoscopic, vaginal, and robotic approaches to radical hysterectomy as well as fertility-sparing radical trachelectomy, are reviewed. The nerve-sparing abdominal radical hysterectomy technique allows for a significant reduction in postoperative bladder morbidity. Radical vaginal hysterectomy with laparoscopic lymph node dissection is a well-recognized technique that offers excellent cure rates without abdominal entry as well as reduced postoperative febrile and gastrointestinal morbidity. Total laparoscopic radical hysterectomy is a minimally invasive alternative to the traditional abdominal radical hysterectomy approach and yields a comparable safety profile with a significant reduction in blood loss and hospital stay. Robotic surgery is becoming more widely accepted in the management of gynecologic cancers, including radical hysterectomy for early cervicalcancer. Young women desiring to bear children in the future may be candidates for fertility preservation options, and the radical trachelectomy operation has been described and performed with abdominal, vaginal, laparoscopic, and robotic techniques. There are a number of surgical options for the treatment of women with early cervicalcancer. The feasibility and safety of some of these techniques have been well established, whereas for others, the oncological outcome data are only preliminary. The decision to use newer techniques should be directed by patient variables as well as the surgeon's training and competence with laparoscopy, robotics, or vaginal surgery. PMID:20014423

Background DNA hypermethylation and histone deacetylation are epigenetic events that contribute to the absence or downregulated expression of different components of the tumor recognition complex. These events affect the processing and presentation of antigenic peptides to CTLs by HLA class-I molecules. In this work evaluated the effect of the DNA hypomethylating agent hydralazine and the histone deacetylase inhibitor valproic acid, on the expression of HLA class-I molecules and on the antigen-specific immune recognition of cervicalcancercells. Methods Cell lines C33A (HPV-), CaSki (HPV-16+) and MS751 (HPV-18+) were treated with hydralazine and valproic acid to assess the expression of HLA class-I molecules by flow cytometry and RT-PCR. Promoter methylation of HLA class-I -A, -B and C, was also evaluated by Methylation-Specific PCR. Primary cervical tumors of four HLA-A*0201 allele patients were typed for HPV and their CTL's stimulated in vitro with the T2 cell line previously loaded with 50 ?M of the HPV peptides. Cytotoxicity of stimulated CTL's was assayed against Caski and MS751 cells pre-treated with hydralazine and valproic acid. Results Valproic acid and hydralazine/valproic acid up-regulated the constitutive HLA class-I expression as evaluated by flow cytometry and RT-PCR despite constitutive promoter demethylation at these loci. Hydralazine and valproic acid in combination but no IFN-gamma hyperacetylated histone H4 as evaluated by ChiP assay. The antigenic immune recognition of CaSki and MS751 cells by CTLs specific to HPV-16/18 E6 and E7-derived epitopes, was increased by VA and H/VA and the combination of H/VA/IFN-gamma. Conclusion These results support the potential use of hydralazine and valproic acid as an adjuvant for immune intervention in cervicalcancer patients whenever clinical protocols based on tumor antigen recognition is desirable, like in those cases where the application of E6 and E7 based therapeutic vaccines is used. PMID:17192185

Radical parametrectomy is indicated in cases of undiagnosed early-stage invasive cervical carcinoma discovered after simple hysterectomy performed for a presumed benign disease process. This radical surgical procedure is rarely performed for benign disease; however, there are some benign conditions such as endometriosis or ovarian remnant syndrome which may require wide excision, including parametria. Traditionally, radical parametrectomy has been performed via laparotomy; however, a minimally invasive approach via laparoscopy has been reported to be feasible and safe. Here we describe the robotic surgical approach to radical parametrectomy. PMID:21860209

Advent of medical image digitalization leads to image processing and computer-aided diagnosis systems in numerous clinical applications. These technologies could be used to automatically diagnose patient or serve as second opinion to pathologists. This paper briefly reviews cervical screening techniques, advantages, and disadvantages. The digital data of the screening techniques are used as data for the computer screening system as replaced in the expert analysis. Four stages of the computer system are enhancement, features extraction, feature selection, and classification reviewed in detail. The computer system based on cytology data and electromagnetic spectra data achieved better accuracy than other data. PMID:24955419

Croatia still has opportunistic screening and the organized national screening has been planned. The European CervicalCancer Prevention Week was held twice in Croatia, in January 2008 and 2009. Within the first one in 2008, information campaign "For All Women" via mass media was held, and women were invited to the organized free gynecological examination and Papanicolaou test (Pap test) in the University Department of Gynecology and Obstetrics, Zagreb University Hospital Center. Following invitation 481 women attended the testing; the median age was 55 years. There were more women aged > or = 50 (n = 353), with the highest participation in the age group 55-59 years (n = 94). Some women came because of subjective symptoms (n = 10), but the majority of them came only for testing (n = 471). According to history of previous cytological testing, 400 women have had > or = 1 negative findings, 71 women have had > or = 1 positive findings, 9 women attended Pap test for the first time, and 1 woman does not know about previous testing. Cervical cytology was abnormal in 35 women (7.28%), the median age was 42 years with the highest proportion in the age group 30-34 years (n = 7); among all of them 21 women (60%) had no abnormal Pap test previously. The findings were: Atypical squamous cells of undetermined significance--ASC-US (n = 9), ASC cannot exclude high-grade squamous intraepithelial lesion--ASC-H (n = 1), cervical intraepithelial neoplasia--CIN 1 (n = 13), CIN 2 (n = 1), CIN 3 (n = 6), carcinoma planocellulare (n = 2), atypical glandular cells--AGC-favor reactive endocervical cells (n = 3). Among women aged < or = 49 there were 20.47% abnormal findings and among those aged > or = 50, 2.55%. According to 21 positive Pap tests previously, among women aged < or = 49 there were 30.71% while among those aged > or = 50 there were 9.07%. Within the European CervicalCancer Prevention Week in 2009, employed women from one national company were invited by internal information to the same procedure. A smaller group of younger asymptomatic women came for testing (n = 53), median age 39 years. According to history of previous cytological testing, 50 women have had > or = 1 negative findings, 3 women have had > or = 1 positive findings. In this study, Pap test was positive in 3.77% (n = 2). National screening programme should be focused on the participation of all personally invited women, especially younger age groups and under-screened women. Well designed information campaign should be implemented in national screening programme. PMID:20698138

Epithelial-mesenchymal transition (EMT) plays an important role in cancer invasion and metastasis by enabling cancercells to depart from the primary tumor, invade surrounding tissue and disseminate to distant organs. The existence and function of EMT in cervicalcancer is poorly understood. Placental growth factor (PLGF) has been shown to associate with EMT in various cancers. However, whether PLGF is involved in EMT in cervicalcancer remains unclear. Thus the present study examined the relationship between PLGF expression and EMT-related proteins in 110 cervical lesions samples. We detected that PLGF was expressed in 61.8% cervical lesion sections. In addition, PLGF expression is positively correlated with low expression level of E-cadherin and high expression level of vimentin. Serum samples and cervical lavage samples were collected from patients with pre-invasive and invasive lesion of uterine cervix or normal control group, the PLGF levels were determined by enzyme-linked immunosorbent assay (ELISA). We found that a significantly high level of PLGF could be detected both in serum and vaginal lavage compared with normal women group, and there is no significant difference between serum and lavage in PLGF level. In addition, whatever in lavage or in serum, the PLGF level in stage I and II was significantly higher than it in CINIII or cancer in situ. However, there is no significant difference between the stage I and stage II; we also found that exogenous PLGF promotes molecular changes of epithelial-mesenchymal transition (EMT) in siha cells. In addition, application of a specific EKR1/2 inhibitor could reverse the effects of PLGF. These findings suggested that PLGF could regulate the expression of EMT-related proteins and promote migration of siha cells through ERK/MAPK signaling pathway. Therapies that targets PLGF/Flt-1/ERK/MAPK signaling pathway may be beneficial in treatment of cervicalcancer.

The aim of the present study was to evaluate the efficacy of picosecond pulsed electric fields (psPEF) on a cervicalcancer xenograft. Human cervicalcancer xenografts were established in nude mice by transplantation of HeLa cells, and the tumors were then treated with psPEF. The histological changes were observed by hematoxylin?eosin staining and transmission electron microscopy. The rate of tumor cell apoptosis was determined using a terminal deoxynucleotidyl?transferase?mediated dUTP nick end labeling assay. The mitochondrial transmembrane potential of the tumor cells was detected by laser scanning confocal microscopy, and the activity of caspase?3, ?8, ?9 and ?12 was determined. The inhibitory rate seven days post?psPEF treatment was also calculated. The results showed that exposure to psPEF led to an increased rate of apoptosis, collapse of mitochondrial transmembrane potential, and activation of caspases. The inhibitory rate was 9.11% at day 7. The results of the present study indicate that psPEF may induce apoptosis in a cervicalcancer xenograft through the endoplasmic reticulum stress and caspase?dependent signaling pathways. PMID:25405328

The aim of the present study was to evaluate the efficacy of picosecond pulsed electric fields (psPEF) on a cervicalcancer xenograft. Human cervicalcancer xenografts were established in nude mice by transplantation of HeLa cells, and the tumors were then treated with psPEF. The histological changes were observed by hematoxylin-eosin staining and transmission electron microscopy. The rate of tumor cell apoptosis was determined using a terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assay. The mitochondrial transmembrane potential of the tumor cells was detected by laser scanning confocal microscopy, and the activity of caspase-3, -8, -9 and -12 was determined. The inhibitory rate seven days post-psPEF treatment was also calculated. The results showed that exposure to psPEF led to an increased rate of apoptosis, collapse of mitochondrial transmembrane potential, and activation of caspases. The inhibitory rate was 9.11% at day 7. The results of the present study indicate that psPEF may induce apoptosis in a cervicalcancer xenograft through the endoplasmic reticulum stress and caspase-dependent signaling pathways. PMID:25405328

This paper aims at to present the integration of the files of the Brazilian CervicalCancer Information System (SISCOLO) in order to identify all women in the system. SISCOLO has the exam as the unit of observation and the women are not uniquely identified. It has two main tables: histology and cytology, containing the histological and cytological examinations of women, respectively. In this study, data from June 2006 to December 2009 were used. Each table was linked with itself and with the other through record linkage methods. The integration identified 6236 women in the histology table and 1,678,993 in the cytology table. 5324 women from the histology table had records in the cytology table. The sensitivities were above 90% and the specificities and precisions near 100%. This study showed that it is possible to integrate SISCOLO to produce indicators for the evaluation of the cervicalcancer screening programme taking the woman as the unit of observation. PMID:22341207

Objective: To explore the relationship between serum selenium and cervicalcancer. Methods: We conducted a case–control study of cervicalcancer in five areas around Birmingham, AL; Chicago, IL; Denver, CO; Miami, FL; and Philadelphia, PA. Community controls were selected by random-digit dialing and were matched to invasive cervicalcancer cases by age, race\\/ethnicity, and telephone exchange. Serum selenium was determined

Since 1976 a clinical trial has been conducted to test the feasibility, the potential, and to develop methods for using the neutron-emitting radioactive isotope, californium-252 (Cf-252), for the treatment of cervicalcancer. A total of 218 patients were treated in the initial study period from 1976 until 1983. The trials initially treated advanced cervicalcancer patients using different doses and schedules; they were extended to include unfavorable presentations of Stages 1 and 2 because of favorable results in the initial trials. The authors began to treat patients with Stage IB bulky or barrel-shaped tumors and the majority were treated with both radiation and hysterectomy. Actuarial survival was determined for Stage IB disease and was 87% at 5 years and 82% at 10 years. For those tested with preoperative radiation it was 92% at 5 and 87% at 10 years. For Stage 2, it was 62% 5 years and 61% at 10. Survival 5 years after combined radiation and surgical therapy for Stage 2 disease was 68%. For Stage 3, it was 33% at 5 years and 25% at 10. However, 5-year survival using the early neutron implant was 46% versus approximately 19% for delayed Cf-252 or cesium 137. Different schedules and sequences of neutrons and photons greatly altered outcome. Neutron treatment before external photon therapy was better for all stages of disease. Only about 5% of all patients developed complications after neutron therapy. No hematologic or mesenchymal second tumors were observed. Neutron brachytherapy was found to be very effective for producing rapid response and greatly improved local control of bulky, barrel, or advanced cervicalcancers. The clinical trial identified and evolved schedules, doses, doses per session, and developed methods different from standard photon therapy but highly effective for local control and cure of cervicalcancers of all stages.

The objectives of this study were to investigate the awareness, motivation, and readiness of medical staff to take part in a cervicalcancer screening program (CSP), with the ultimate aim of increasing the response rate to invitation letters and improving CSP effectiveness and coverage. Certified gynecologists (GYNs) and general practitioners (GPs) practicing in the national and private healthcare systems in Latvia were given specially designed multiple-choice questionnaires. Of 213 questionnaires distributed to GYNs, 74% were completed (32% response rate of all 486 GYNs in Latvia). GPs were sent 933 questionnaires, 24% were returned (15% response rate of all 1,455 GPs in Latvia). GPs registered for 10 years or more knew significantly less about prevention and screening for cervicalcancer compared to GYNs registered for the same amount of time (p = 0.05). This finding was not seen among the GYNs (p = 0.782). In the entire study group, the average score for correct answers was 5.97 (SD 2.602). Knowledge in the GP group was significantly lower (5.03, SD 2.243) than in the GYN group (7.22, SD 2.527, p < 0.001). Irrespective of specialization and place of work, knowledge was evaluated as poorer with an increase in age (RR = 0.950; p < 0.001). The knowledge, awareness, and perception of GYNs regarding cervicalcancer prevention and screening in Latvia is sufficient but not good, and that of GPs is poor. Doctors would like to learn more about preventing cervicalcancer. PMID:25527039

Local delivery of cancer chemotherapeutics enables sustained drug levels at the site of action thereby reducing systemic side effects. A novel insertable polymeric drug delivery system for cervicalcancer treatment is presented. Cisplatin, the first line of therapy employed for cervicalcancers, was incorporated in a poly(ethylene-co-vinyl acetate) (EVAc) device that is similar to those currently used for vaginal contraceptive

Background: About 80% of cervicalcancers occur in less- developed countries. This disproportionate burden of cervi- cal cancer in such countries is due mainly to the lack of well-organized screening programs. Several cervicalcancer screening strategies have been proposed as more cost- effective than cytology screening. We compared the costs and benefits of different strategies and their effectiveness in saving

To evaluate safety, feasibility and the improvement of surgical method of laparoscopic extensive hysterectomy and pelvic lymph node dissection in patients with early-stage cervicalcancer. Clinical data were prospectively collected from patients with IA2-IIA cervicalcancer who underwent laparoscopic extensive hysterectomy (n1=22) and laparotomy (n2=23) in Department of Obstetrics and Gynecology in the Subei People’s Hospital from June 2010 to August 2013. The successful rates in two groups of operation were 100%. Blood loss, postoperative hospital stay, complication rate, postoperative recovery of gastrointestinal tract and bladder function of the laparoscopy group of the laparoscopic group were all better than those of the laparotomy group, and there were significant differences (all P < 0.05). But in the laparoscopy group, the operative time was longer than the laparotomy group with statistical significance (P < 0.05). There was no statistically significant difference in the number of excised lymph nodes and the duration time of postoperative urinary catheterization between the two groups (P > 0.05). Laparoscopic extensive hysterectomy and pelvic lymph node dissection can fully meet the requirement of laparotomy. It has the properties of minor trauma and rapid recovery. The clinical efficacy is superior to laparotomy surgery. The results indicated laparoscopic is an ideal method for the treatment of early cervicalcancer. PMID:24995098

Thyroid cancer is the most common endocrine malignancy. Recently, controversy has focused on the management of lymph node metastases, which represent approximately 90% of disease recurrences and may require considerable time, effort, and resources to diagnose and treat. Neck dissections play an essential role in the management of head and neck cancer. A modified radical neck dissection (MND) refers to resection of the lymph nodes in levels II through V and often including the central nodes in level VI. When performing modified neck dissection, we recommend to protect more reserved cervical plexus. The purpose is to better protect patient’s neck skin feeling. PMID:25083485

MicroRNAs (miRNAs) play important roles in various biological processes and are closely associated with the development of cancer. In fact, aberrant expression of miRNAs has been implicated in numerous cancers. In cervicalcancer, miR-203 levels are decreased, although the cause of this aberrant expression remains unclear. In this study, we investigate the molecular mechanisms regulating miR-203 gene transcription. We identify the miR-203 transcription start site by 5’ rapid amplification of cDNA ends and subsequently identify the miR-203 promoter region. Promoter analysis revealed that IRF1, a transcription factor, regulates miR-203 transcription by binding to the miR-203 promoter. We also demonstrate that miR-203 targets the 3’ untranslated region of BANF1, thus downregulating its expression, whereas miR-203 expression is driven by IRF1. MiR-203 is involved in cell cycle regulation and overexpression of miR-203 suppresses cervicalcancercell proliferation, colony formation, migration and invasion. The inhibitory effect of miR-203 on the cancercells is partially mediated by downregulating its target, BANF1, since knockdown of BANF1 also suppresses colony formation, migration and invasion. PMID:25658920